Search

This study was conducted to determine the phenolic compounds that may be utilized as chemotaxonomic study to identify some phenolic compounds concentration that are useful for pharmaceutical purposes from 5 taxa belongs to the Brassicaceae family which are; Cardaria draba (L.) Desv., Lepidum aucheri Boiss., Sisymbrium irio L., Sisymbrium officinale (L.) Scop., and Sisymbrium septulatum DC. Leaves powder of these taxa were collected and analyzed by High-performance liquid chromatography (HPLC). The results identified 9 phenolic compounds, chlorogenic acid, cinnamic acid, ferulic acid, genstic acid, kaempferol, p-coumaric acid, protocatechuic acid, sinapic acid, and vanillic acid. The results showed that the genus Lepidium aucheri had the highest concentration of 4 phenolic compounds, cinnamic acid, genstic acid, p-coumaric acid, and sinapic acid with concentration of (37.2, 80.79, 62.91, and 37.10µg/ ml) respectively. On the other hand, the genus Cardaria draba showed the lowest concentration of 3 phenolic compounds, cinnamic acid, p- coumaric acid, and protocatechuic acid, and doesn't have 2 phenolic compounds, genstic acid and kaempferol. This variation in the phenolic concentrations might be due to the genotype and plant growth stage differences. The results of this study provide a source for bioactive compounds to future studies. http://dx.doi.org/10.25130/tjps.23.2018.027

Enzymatic decarboxylation and carboxylation are emerging as prospective processes to produce high-value compounds under mild conditions. Ferulic acid decarboxylase Fdc1 catalyzes broad substrate tolerance against α, β-unsaturated carboxylic acids, and provides green routes for carbon dioxide fixation with the reversible carboxylation, while the activity of the enzyme is limited by the indispensable cofactor prenylated flavin (prFMN), which is unstable and is rarely detected in nature. In this study, a prFMN efficient synthesis route was built using six exogenous enzymes introduced into E. coli cells, leading to the construction of a powerful cell catalyst named SC-6. Based on the metabolic analysis, the results indicated that the reduction of FMN to FMNH2 was the bottleneck in prFMN synthesis pathway, and introducing FMN reductase increased the production of prFMN 3.8-fold compared with the common flavin prenyltransferase UbiX overexpression strain. Using SC-6 cell catalyst, the decarboxylation activity of Fdc1 increased more than 20 times with cinnamic acid and 4-acetoxycinnamic acid as substrates. Furthermore, the reversible carboxylation reaction was carried out, and the cell catalyst presented 20 times carbon dioxide fixation activity using styrene to produce cinnamic acid. Finally, the maximum yield of cinnamic acid catalyzed by SC-6 achieved 833.68 ± 34.51 mM·mg−1 in two hours. The constructed prFMN pathway in vivo provides fundamentals for efficient decarboxylation and carbon fixation reactions catalyzed by prFMN-dependent enzymes.

The role of Cinnamic acid derivatives as antioxidants, antimicrobial agents, antidiabetic drugs, anticancer drugs etc. is well reported. A thorough literature search revealed that the substitution on carboxylic acid group of Cinnamic acids by different amines imparts the potent conjugates. The quest for the design of effective anti-inflammatory drugs is still the primal focus of several research works world-wide owing to the side effects associated with the existing drugs. The side effects of the existing drugs are associated with the presence of the free carboxyl group in the molecules. In the present work, Cinnamic acid was reacted with various cyclic amines in presence of coupling agent to obtain the corresponding amide derivatives which were evaluated for anti-inflammatory activity using in vitro methods.

The aim of the study is to evaluate the effect of 4-hydroxy-3,5- di-tertbutyl cinnamic acid on the change in mitochondrial function under conditions of experimental cerebral ischemia in rabbits. The study was performed on 48 male rabbits, which were used for modeling permanent cerebral ischemia by occlusion of the common carotid arteries. The test compound was administered before modeling ischemia for 14 days and after the occurrence of reproducing ischemia, in a similar time interval. After that, neurological deficit and the parameters of mitochondrial respiration, the intensity of anaerobic processes, the latent opening time of the mitochondrial permeability transition pore, the value of the mitochondrial membrane potential and the concentration of caspase – 3 were determined. The administration of 100 mg/kg of 4-hydroxy-3,5-di-tertbutyl cinnamic acid into the animals reduced neurological deficit and restored the mitochondrial membrane potential. Prophylactic administration of 4-hydroxy- 3,5-di-tertbutyl cinnamic acid, contributed to an increase in ATPgenerating ability, the maximum level of respiration and respiratory capacity by 4.1 times (p

Side reaction pathways are observed to occur between antioxidants and peroxide during the processing of multiple resin grades mediated by controlled peroxide-induced degradation of impact polypropylene. In the present work, the reaction mechanism and main by-products between antioxidants and peroxides were investigated. The results demonstrate that peroxides greatly accelerate the decomposition reactions, and the free radicals formed from peroxide decomposition react with, for example, the antioxidant AO1010 to produce dehydrogenation of phenyl propionic unit(s) at the α position (cinnamic acid ester moiety), which generates a conjugated system leading to the increased color of the product. It is the first time to confirm the cinnamic acid moiety’s existence and report its NMR data. Further, this work confirms the dehydrogenation mechanism by comparison with different sterically hindered phenolic antioxidants. It also systematically summarizes the oxidation and degradation mechanism of AO168 and AO1010 under air and peroxide environments, respectively. Based on present study, clear guidelines are obtained to improve the quality of polymeric products, especially the appearance and stability, during product development.

The genus Fuchsia is generally used in herbal preparations to treat conditions caused by microorganisms. Based on the popular use of this type of plants, the objective of this study was to obtain sequential extracts of increasing polarity from the branches of Fuchsia lycioides by maceration at room temperature and by the Soxhlet method at 60ºC, to later evaluate the antifungal capacity of the extracts against different clinical isolates of the Candida genus. The ethyl acetate extract exhibited strong anti-fungal activity, selectively inhibiting C. albicans strains with MIC and CMF values of 10 and 15 µg/mL, respectively; comparable with the drug itraconazole®. The analysis of the extract by GC-MS showed a high concentration of terpenoids (mainly phytol) and phenylpropanoids (mainly cinnamic acid), possibly responsible for the antifungal activity of the ethyl acetate extract of F. lycioides.

• Penicillium chrysogenum CCDCA10746 secretome (SPc) produced using raw sugarcane bagasse was used to hydrolyse the hydrothermally pretreated sugarcane bagasse, in order to solubilise xylan to produce xylose with the conversion rate of 67%. The secretome was active in a wide pH range and exhibits increased thermostability (t1/2 8 h) than purified PcX2, a 23 kDa endo-β-1,4-xylanase of GH11 family, identified by mass spectrometry and zymogram. Xylanolytic activity was sensitive to Cu+2 and Zn+2 ions. In trials where enzymes were exposed to lignin-derived phenolic compounds: vanillin, cinnamic acid, and 4-hydroxy-benzoic acid inhibited the 70% activity of xylanase. On contrary, both enzymes showed resistance for tannic acid, additionally PcX2 was resistant to p-coumaric and SPc to gallic acid. PcX2 showed a binding affinity of KM 0.53 mg/mL and Vmax 0.21 U/mg for xylan oat spelt. Ionization of histidine appeared to be a crucial event in substrate binding and catalysis of PcX2 since decrease in fluorescence intensity and optimum activity was observed at pH 6.0.

Cinnamic acid is a plant metabolite with antimicrobial, anticancer, and antioxidant properties. Its synthetic derivatives are often more effective in vitro than parent compounds due to stronger biological activities. In our study, we synthesized ten new N–(4–chloro–2–mercapto–5–methylphenylsulfonyl)cinnamamide derivatives, containing two pharmacophore groups: cinnamic acid moiety and benzenesulfonamide. The antimicrobial activity of the obtained compounds was estimated using different types of Gram-positive and Gram-negative bacteria, fungus species of Candida albicans, as well as clinical strains. The compounds were evaluated on biofilm formation and biofilm formed by Staphylococcus clinical strains (methicillin–resistance S. aureus MRSA and methicillin–resistance coagulase–negative Staphylococcus MRCNS). Furthermore, blood bacteriostatic activity test was performed using S.aureus and S. epidermidis. In cytotoxic study, we performed in vitro hemolysis assay on domestic sheep peripheral blood and MTT [3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide] assay on human cervical HeLa, ovarian SKOV-3, and breast MCF-7 cancer cell lines. We also estimated antioxidant activity of ten compounds with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′–azino–bis(3–ethylbenzthiazoline–6–sulfonic acid) (ABTS) assays. Our results showed a significant antimicrobial activity of the compounds. All of them were active on Staphylococcus and Enterococcus species (MIC was 1–4 µg/mL). The compounds 16d and 16e were the most active on staphylococci clinical strains and efficiently inhibited the biofilm formation and biofilm already formed by the clinical staphylococci. Moreover, the hemolytic properties of the tested compounds occurred in higher quantities (>32.5 µg/mL) than the concentrations that inhibited both the growth of bacteria in the blood and the formation and growth of biofilm. The results of MTT assay showed that compounds 16c, 16d, 17a, and 17d demonstrated the best activity on the cancer cells (the IC50 values were below 10 µg/mL). Compound 16f was the least active on the cancer cells (IC50 was > 60 µg/mL). Antiradical tests revealed that compounds 16f and 17d had the strongest antioxidant properties within the tested group (IC50 was 310.50 ± 0.73 and 574.41 ± 1.34 µg/mL in DPPH, respectively, and 597.53 ± 1.3 and 419.18 ± 2.72 µg/mL in ABTS assay, respectively). Our study showed that the obtained cinnamamide derivatives can be used as potential antimicrobial therapeutic agents.

Supervisor:金子 達雄, 先端科学技術研究科, 博士

The severity of infectious diseases associated with the resistance of microorganisms to drugs highlights the importance of investigating bioactive compounds with antimicrobial potential. Therefore, nineteen synthetic cinnamides and cinnamates having a cinnamoyl nucleus were prepared and submitted for the evaluation of antimicrobial activity against pathogenic fungi and bacteria in this study. To determine the minimum inhibitory concentration (MIC) of the compounds, possible mechanisms of antifungal action, and synergistic effects, microdilution testing in broth was used. The structures of the synthesized products were characterized with FTIR spectroscopy, 1 H-NMR, 13 C-NMR, and HRMS. Derivative 6 presented the best antifungal profile, suggesting that the presence of the butyl substituent potentiates its biological response (MIC = 626.62 μM), followed by compound 4 (672.83 μM) and compound 3 (726.36 μM). All three compounds were fungicidal, with MFC/MIC ≤ 4. For mechanism of action, compounds 4 and 6 directly interacted with the ergosterol present in the fungal plasmatic membrane and with the cell wall. Compound 18 presented the best antibacterial profile (MIC = 458.15 μM), followed by compound 9 (550.96 μM) and compound 6 (626.62 μM), which suggested that the presence of an isopropyl group is important for antibacterial activity. The compounds were bactericidal, with MBC/MIC ≤ 4. Association tests were performed using the Checkerboard method to evaluate potential synergistic effects with nystatin (fungi) and amoxicillin (bacteria). Derivatives 6 and 18 presented additive effects. Molecular docking simulations suggested that the most likely targets of compound 6 in C. albicans were caHOS2 and caRPD3, while the most likely target of compound 18 in S. aureus was saFABH. Our results suggest that these compounds could be used as prototypes to obtain new antimicrobial drugs.

The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-1 were obtained for the essential oil and 4.36 μg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-1 for the essential oil of citronella and 86.30 μg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.

Background In this study, flowers of nine mullein species (Verbascum erianthum, V. songaricum, V. speciosum, V. szovitsianum, V. stachydiforme, V. sinuatum, V. haussknechtianum, V. cheirantifolium, and V. saccatum) were collected from Iran. Total flavonoid content (TFC), antioxidant activity, total carotenoid (TCC) and β-carotene content and the amount of phenolic compounds were determined in all of the collected mullein species. Quantitative analysis of phenolic compounds was performed by using HPLC-DAD. Results V. saccatum and V. songaricum, in particular, were found rich in total flavonoid so exhibit the highest antioxidant capacity. The HPLC-DAD analysis revealed that V. erianthum possesses the highest amount of caffeic acid (0.022 g kg-1 DW), chlorogenic acid (2.649 g kg-1 DW), p-coumaric acid (0.253 g kg-1 DW), and apigenin (0.066 g kg-1 DW) and the highest amount of gallic acid (0.134 g kg-1 DW), rutin (5.254 g kg-1 DW), quercetin (1.303 g kg-1 DW), and cinnamic acid (1.031 g kg-1 DW) content were observed in V. saccatum. Our results demonstrate the considerable variations in the TFC, antioxidant activity, TCC and β-carotene content among the mullein species. Conclusions The findings of this study provide remarkable information for schematization breeding strategies, and for choosing the best species with high phenolic compounds content to produce natural antioxidant compounds as a medicinal plant for the medical uses and pharmaceutical industries. This article is protected by copyright. All rights reserved.

Cinnamic acid and cinnamaldehyde may be obtained from renewable plant bio-mass, Cinnamon plants, therefore these compounds should be considered as bio-based platform chemicals for synthesis of novel substances. This review describes recent achievements in organic synthesis based on transformations of cinnamaldehyde, cinnamic acid and its derivatives, focusing, mainly, on the preparation of biologically active compounds. Reactions of these cinnamic derivatives may proceed both onto carbon-carbon double bond and carbonyl group that allows obtaining a wide variety of organic compounds having high synthetic importance and different practically valuable properties, including biological activity.

The antioxidant properties of methanol extract of above-ground parts of Alyssum virgatum, an endemic plant, were analyzed. Together with their total phenolic, flavonoid, and antioxidant capacities, their effects on reactive oxygen species were determined by experimental methods. The methanol extracts of A. virgatum plant appeared to exhibit in-vitro antioxidant activity. In particular, the extract of the plant was found to have a scavenging effect against hydrogen peroxide and hydroxyl radical. Total phenolic content was found to be 161.25 mg gallic acid per gram dry material. Total flavonoid content was found to be 119.89 mg quercetin per gram dry material. Total antioxidant capacity was determined as 94.92 mM α-tocopherol acetate per gram dry material. Moreover, the amount of the extract that caused 50% inhibition of hydrogen peroxide and hydroxyl radical was assayed as 29.24 mg mL− 1 and 46.04 mg mL− 1, respectively. Addition to the experimental studies, DFT, molecular docking, and ADME calculations were performed to determine antioxidant, biological activity, and drug properties of two main phenolic components of A. virgatum which are cinnamic acid and ferulic acid. DFT calculations were executed at B3LYP/6–311 + + G(d,p) level in Gaussian 16 software. The HAT, SET-PT, SPLET mechanisms, and the spin density analyses of the main components were investigated in detail. Molecular docking studies of the investigated main components were executed on the antioxidant proteins in Schrodinger 2020–3 program. Additionally, ADME properties of the mentioned main components were determined via QikProp module in the Schrodinger software. All theoretical studies showed that ferulic acid had better antioxidant, biological, and drug activities than cinnamic acid.

Previously undescribed species of Limosilactobacillus fermentum isolated from wholemeal buckwheat sourdough were identified by MALDI-TOF/MS and 16S rRNA analysis. The metabolism of 6 hydroxycinnamic acids by L. fermentum 6P1, 6P2 and 7P2 strains provided mostly o-, m-, p-dihydrocoumaric, dihydroferulic, dihydrocaffeic and dihydrosinapic acids. The ratio of hydroxyphenylpropionic acids to 4-vinylphenols was strain-to-strain specific. Decarboxylation of free cinnamic acid to potentially toxic styrene was low (1.8–23.9 mol. %) in all Limosilactobacillus strains tested. At a concentration of 13.6 mmol/L, reduced p-dihydrocoumaric and dihydroferulic acids were shown to cause less growth inhibition than their precursors, while specific growth rates μ increased significantly. L. fermentum POH with the highest sensitivity to phenolic acids exhibited the lowest ability to reduce hydroxycinnamic acids (11.8–44.5%) by phenolic acid reductase. Metabolomic experiments with chemically labelled D-glucose-d12 provided a deeper insight into electron transfer to polyphenols as the final acceptor. To the best of our knowledge, deuterium transfer to dideuteroferulic acid was observed for the first time.

P-Coumaric acid (p-CA) is a hydroxycinnamic acid, an organic compound that is a hydroxyl derivative of cinnamic acid. P-CA is the most abundant isomer in nature and can be found in a wide variety of edible plants such as fungi, peanuts, navy beans, tomatoes, carrots, basil, and garlic. Recently, the therapeutic properties of p-CA have received a great deal of attention from scientific society. Here, we described the medicinal effects of p-CA on various pathological conditions. This review was performed via evaluating PubMed reported studies from January 2010 to January 2020. Also, reference lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies, in vitro studies, and controlled trials (CTs) on p-CA were acceptable. However plant extract studies without indication of main active substances were excluded due to the considerable diversities and heterogeneities. According to recent evidence regarding the beneficial effects of p-CA, numerous diseases such as nephropathies, cardiovascular diseases, neuroinflammatory diseases, liver diseases, cancers, and some metabolic disorders could potentially be controlled by this natural herb. Interestingly, autophagy is a novel molecular mechanism involved in the crosstalk between classic effects of p-CA and introduces alternative therapeutic pathways for this compound. Much work remains in clarifying the main therapeutic properties among the various p-CA effects; these will be the subject of forthcoming work, resulting in presenting further mechanism of action.

The Pleurotus florida is recognized as a medicinal and edible mushroom and the present study intends to reveal the active isomeric molecules from this mushroom. The P. florida was cultivated using different nutrient supplements: groundnut husk, maize powder, horse gram powder and coconut oil-cake powder. Horse gram supplement showed the higher mushroom yield and henceit was used for the cultivation of P. florida. Methanolic extract of P. florida was found to be efficient in antioxidant activity among ethanol, aqueous, ethyl acetate and hexane extracts. The bioactive fraction 3-methoxy-4-hydroxy cinnamic acid (PF5) was isolated and purified from the methanolic extract of P. florida by column chromatography, thin layer chromatography (TLC) and gas chromatography-mass spectrum (GC-MS) and further it was characterized by Nuclear magnetic resonance (NMR). The PF5 was tested for its DPPH and reducing power assays, and the IC50 values were found to be 21.7 µg/mL and 105 µg/mL, respectively. We found that the cytotoxic effect of 3-methoxy-4-hydroxy cinnamic acid was tested against the lung cancer cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), sulphorodamine B (SRB) and trypan blue assays which exhibited a higher cytotoxic effect (CTC50, 645 µg/mL). These results suggested that 3-methoxy-4-hydroxy cinnamic acid from P. florida could be explored as a novel and potent natural antioxidant and cancer preventive agent, alternative to existing synthetic molecules.

Cinnamic acid, isolated from cinnamon bark, is a natural product with excellent bioactivity, and it effectively binds with cyclohexanedione to form novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors. According to the active sub-structure combination principle, a series of novel 3-hydroxy-2-cinnamoyl-2-en-1-one derivatives were designed and synthesized. The title compounds were characterized by infrared, 1H NMR, 13C NMR, and HRMS. The in vitro inhibitory activity of AtHPPD verified that compound II-13 showed the most activity with a half-maximal inhibitory concentration (IC50) value of 0.180 μM, which was superior to that of mesotrione (0.206 μM) in vitro. The preliminary herbicidal activity tests demonstrated that some compounds had good herbicidal activity especially compound II-13 at a concentration of 150 g ai/ha. The binding mode of AtHPPD through molecular docking indicated that two oxygens of compounds II-13 formed bidentate interactions with metal ions, and the benzene ring formed π-π accumulation effects with Phe-381 and Phe-424. The results of molecular dynamics simulations showed that compound II-13 exhibited a more stable binding ability with AtHPPD than mesotrione. This study provided insights into the development of natural and efficient herbicides in the future.

A new ceramide, named cladamide (1), in addition to cinnamic acid (2), para-coumaric acid (3), stigmasterol-3-O-β-D-glucoside (4), and uracil (5), was isolated from the white beans culture of Cladosporium cladosporioides, a marine-derived endohpytic fungus isolated from the leaves of the mangrove, Avicennia marina (Forssk.) Vierh. Structure elucidation of compound 1 was established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC50 = 0.057 ± 0.003 µM), followed by compound 4 (IC50 = 0.068 ± 0.003 µM) and compound 1 (IC50 = 0.099 ± 0.005 µM) compared to donepezil, the positive control, (IC50 = 0.044 ± 0.002 µM). Compounds 2 and 5 showed lower activity (IC50 = 0.182 ± 0.009 and 0.236 ± 0.012 µM, respectively). The results were further validated by molecular docking study.

4-Hydroxybenzoic acid (4-HBA) is a common organic compound that is prevalent in the environment, and the persistence of 4-HBA residues results in exertion of pollution-related detrimental effects. Bioremediation is an effective method for the removal of 4-HBA from the environment. In this study, two bacterial strains FZ-5 and FZ-8 capable of utilizing 4-HBA as the sole carbon and energy source under anaerobic conditions were isolated from marine sediment samples. Phylogenetic analysis identified the two strains FZ-5 and FZ-8 as Acinetobacter johnsonii and Klebsiella oxytoca, respectively. The strains FZ-5 and FZ-8 degraded 2000 mg·L−1 4-HBA in 72 h with degradation rates of 71.04% and 80.10%, respectively. The optimum culture conditions for degradation by the strains and crude enzymes were also investigated. The strains FZ-5 and FZ-8 also exhibited the ability to degrade other lignin-derived compounds, such as protocatechuic acid, cinnamic acid, and vanillic acid. Immobilization of the two strains showed that they could be used for the bioremediation of 4-HBA in an aqueous environment. Soils inoculated with the strains FZ-5 and FZ-8 showed higher degradation of 4-HBA than the uninoculated soil, and the strains could survive efficiently in anaerobic soil. This is the first report of 4-HBA-degrading bacteria, belonging to the two genera, which showed degradation ability under anaerobic conditions. This study expound the strains could efficiently degrade 4-HBA in anaerobic soil and will help in the development of 4-HBA anaerobic bioremediation systems.

There is a lack of effective antibacterial agents against rice bacterial leaf streak and leaf blight. Cinnamic acid derivatives containing the 1,3,4-oxadiazole moiety were synthesized, and their antibacterial activities against Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo) were evaluated. Based on the three-dimensional quantitative structure-activity relationship (3D-QSAR) model, compound 31 with better antibacterial activity against Xoc was designed and synthesized, and the 50% effective concentration (EC50) value was 0.2 mg/L. The curative and protective activities of compound 31 against rice bacterial leaf streak at 100 mg/L were 39.5 and 35.4%, respectively, which were higher than those of thiodiazole copper (28.4 and 20.7%, respectively). The antibacterial activity of compound 31 against rice bacterial leaf streak is closely associated with the activity of related defensive enzymes and the increase in glutathione metabolism.

In this study, cinnamic acid (CA) conjugated hydroxypropyl chitosan (HPCS) derivatives (HPCS-CA) with different degrees of substitution (DS) were successfully synthesized. The reaction was divided into two steps: the first step was to modify chitosan (CS) to HPCS, and the second step was to graft CA onto HPCS. Structural characterization and properties were carried out employing elemental analysis, Fourier transform infrared (FT–IR) spectroscopy, ultraviolet–visible (UV–vis) spectroscopy, nuclear magnetic resonance (NMR) spectra, X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The solubility test revealed the better water solubility of derivatives than CS. In addition, in vitro antibacterial and antibiofilm tests were performed. As expected, HPCS-CA derivatives exhibited good antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The MIC and MBC of HPCS-CA derivatives could reach 256 μg/mL and 512 μg/mL, respectively. Confocal laser scanning microscopy (CLSM) analysis proved the inhibitory effect of HPCS-CA derivatives on S. aureus and E. coli biofilms by disrupting the formation of biofilms, reducing the thickness of biofilms, and the number of live bacteria. These results suggest the potential applicability of HPCS-CA derivatives in the treatment of biofilm-associated infections and provide a practical strategy for the design of novel CS-based antibacterial materials.

We designed colon-targeted trans-cinnamic acid (tCA) and synthesized its conjugates with glutamic acid (tCA-GA) and aspartic acid (tCA-AA). We evaluated the anti-colitic activity of colon-targeted tCA using a dinitrobenzenesulfonic acid-induced rat colitis model. The conjugates lowered the distribution coefficient and Caco-2 cell permeability of tCA and converted to tCA in the cecum, with higher rates and percentages with tCA-GA than with tCA-AA. Following oral gavage, tCA-GA delivered a higher amount of tCA to the cecum and exhibited better anti-colitic effects than tCA and sulfasalazine (SSZ), which is the current treatment for inflammatory bowel disease. In the cellular assay, tCA acted as a full agonist of GPR109A (EC50: 530 µM). The anti-colitic effects of tCA-GA were significantly compromised by the co-administration of the GPR109A antagonist, mepenzolate. Collectively, colon-targeted tCA potentiated the anti-colitic activity of tCA by effectively activating GPR109A in the inflamed colon, enabling tCA to elicit therapeutic superiority over SSZ.

The phenylpropanoid cinnamic acid (CA) is a plant metabolite that can occur under a trans- or cis-form. In contrast to the proven bioactivity of the cis-form (c-CA), the activity of trans-CA (t-CA) is still a matter of debate. We tested both compounds using a submerged rice coleoptile assay and demonstrated that they have opposite effects on cell elongation. Notably, in the tip of rice coleoptile t-CA showed an inhibiting and c-CA a stimulating activity. By combining transcriptomics and (untargeted) metabolomics with activity assays and genetic and pharmacological experiments, we aimed to explain the underlying mechanistic processes. We propose a model in which c-CA treatment activates proton pumps and stimulates acidification of the apoplast, which in turn leads to the loosening of the cell wall, necessary for elongation. We hypothesize that c-CA also inactivates auxin efflux transporters, which might cause a local auxin accumulation in the tip of the coleoptile. For t-CA, the phenotype can partially be explained by a stimulation of cell wall polysaccharide feruloylation, leading to a more rigid cell wall. Metabolite profiling also demonstrated that salicylic acid (SA) derivatives are increased upon t-CA treatment. As SA is a known antagonist of auxin, the shift in SA homeostasis provides an additional explanation of the observed t-CA-mediated restriction on cell growth.

Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3–341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.

We examined the effects of the extracts from two traditional Chinese medicine plants, Cuscuta chinensis and Eucommia ulmoides, on the healthspan of the model organism Caenorhabditis elegans. C. chinensis increased the short-term memory and the mechanosensory response of aged C. elegans. Furthermore, both extracts improved the resistance towards oxidative stress, and decreased the intracellular level of reactive oxygen species. Chemical analyses of the extracts revealed the presence of several bioactive compounds such as chlorogenic acid, cinnamic acid, and quercetin. A fraction from the C. chinensis extract enriched in zingibroside R1 improved the lifespan, the survival after heat stress, and the locomotion in a manner similar to the full C. chinensis extract. Thus, zingibroside R1 could be (partly) responsible for the observed health benefits of C. chinensis. Furthermore, a hydroxygallic acid derivative and the sterol lipid 4-alpha-formyl-stigmasta-7,24(241)-dien-3-beta-ol are abundantly present in the C. chinensis extract and its most bioactive fraction, but hardly in E. ulmoides, making them good candidates to explain the overall healthspan benefits of C. chinensis compared to the specific positive effects on stress resistance by E. ulmoides. Our findings highlight the overall anti-aging effects of C. chinensis in C. elegans and provide first hints about the components responsible for these effects. European Union’s Horizon 2020 research and innovation program Humboldt-University of Berlin, Germany German Research Foundation (DFG) Open Access Publication Fund of Humboldt-Universität zu Berlin

Background: The role of zinc in diabetes has been a subject of considerable interest due to the insulin-mimetic properties associated with this mineral. On the other hand, phenolic acids are known as plant-derived polyphenols with antioxidative and antidiabetic pharmacological credence. Objective: This study was conducted in order to develop a novel therapeutic nutraceutical with an improved and multi-mode antidiabetic and antioxidative pharmacological property using cinnamic acid and Zn(II) mineral framework. Methods: A Zn(II) acetate complex of cinnamic acid was synthesized and characterized using FT-IR and 1HNMR spectroscopy. Cytotoxicity evaluation was done using Chang liver cells and differentiated L6 myotubes. DPPH and ABTS scavenging, as well as Fe3+ reducing effects, were used to evaluate the antioxidant capacity. The antiglycation, as well as α-glucosidase and α-amylase inhibitory properties, were evaluated. Insulin mimetic property was evaluated as glucose uptake in L6 myotubes, while the complex was docked against GLUT-4 and PKB. Results: FTIR and 1HMR suggested that Zn(II) complexed with cinnamic acid through a Zn(O4) coordination mode, thus affording the resulting complex 2 cinnamic acid molecules. Hence, complexation increased (p ˂ 0.05) the antiglycation effect of cinnamic acid (IC50 = 29.3 μM) by 2 folds (IC50 = 13.9 μM). Also, Zn(II) conferred a potent glucose uptake (EC50 = 31 μM) and α-glucosidase inhibitory (IC50 = 59.4 μM) property on cinnamic acid; hence the activity of the complex was 162 and 2.1 folds higher than (p ˂ 0.05) its precursor, respectively. Further molecular docking studies showed that the complex had a stronger interaction with insulin signaling proteins (GLUT-4 and PKB) than its precursor. Interestingly, the complex showed no severe cytotoxicity. Conclusion: Data suggested a structure-activity relationship. Complexation of Zn(II) to cinnamic acid resulted in a complex with improved and multi-facet pharmacological effects, which may be further studied as a safe glycemic control nutraceutical for T2D and glycation-induced complications.

Sweet basil (Ocimum basilicum L.), a well-known medicinal and aromatic herb, rich in essential oils and antioxidants (contributed by phenolics), is widely used in traditional medicine. The biosynthesis of phytochemicals occurs via different biochemical pathways, and the expression of selected genes encoding enzymes involved in the formation of phenolic compounds is regulated in response to environmental factors. The synthesis of the compounds is closely interrelated: usually, the products formed in the first reaction steps are used as substrates for the next reactions. The current study attempted a comprehensive overview of the effect of aromatic amino acid composition (AAAs) in Ocimum basilicum in respect to the expression of genes related to the biosynthesis of phenolic compound and their content. The transcript expression levels of EOMT, PAL, CVOMT, HPPR, C4L, EGS, and FLS increased depending on the AAAs concentration compared to the control plants. The highest mRNA accumulation was obtained in EOMT, FLS, and HPPR in the leaves of sweet basil. The expression of the TAT gene in the leaves significantly reduced in response to all AAAs applications compared to untreated groups and it had the lowest transcript accumulation. Eleven individual phenolic compounds were determined in the basil leaves, and the contents of chicoric acid, methyl chavicol, caffeic acid, and vanillic acid increased depending on administered concentration to control (p

Pregnane derivatives have been studied mainly for their 5α-reductase activity. However, the anti-inflammatory activities of such compounds are still poorly explored. In the search for new anti-inflammatory agents, seven new pregnane derivatives 6a-g, with cinnamic acid esters at C-3 were prepared and fully characterized. The anti-inflammatory activity of compounds was assessed in TPA induced mice ear model. From them, compound 6 b was the most active to reduce edema, with an ED50 of 0.017 mg/ear. Also, Molecular Docking and Molecular Dynamics studies were performed to identify a potential molecular target related to the inflammatory process. The in vivo results suggest that 6 b could be a potent anti-inflammatory compound, while in silico studies suggest its interaction with some critical enzymes in the inflammatory response. Communicated by Ramaswamy H. Sarma.

Fragrances can cause general health issues, and special concerns exist surrounding the issue of skin safety. Cinnamyl alcohol (CAL) is a frequent fragrance contact allergen that has various toxic effects on indiscriminate animals. In the present study, the photodegradation transformation mechanism of CAL and toxicity evolution during this process were examined. The results showed that CAL (50 μM) can be completely degraded after 90-min ultraviolet (UV) irradiation with a degradation rate of 0.086 min-1 . Increased toxicity on bioluminescent bacteria was observed during this process, with lethality increasing from 10.6% (0 min) to 50.2% (90 min) under UV light irradiation. Further, the photodegradation mechanisms of CAL were explored to find the reason behind the increased toxicity observed. Laser flash photolysis and quenching experiments showed that O2•- , 1 O2 , and • OH were mainly responsible for CAL photodegradation, together with 3 CAL* and eaq- . The 5 main photodegradation products were cinnamyl aldehyde, benzaldehyde, benzenepropanal, cinnamic acid, and toluene, as identified using gas chromatography-mass spectrometry and liquid chromatography-quadrupole-time-of-flight-mass spectrometry. Once exposed to air, CAL was found to be easily oxidized to cinnamyl aldehyde and subsequently to cinnamic acid by O2•- - or 1 O2 -mediated pathways, leading to increased toxicity. Benzaldehyde exhibited bioreactive toxicity, increasing the toxicity through • OH-mediated pathways. Theoretical prediction of skin irritation indicated that cinnamyl aldehyde (0.83), benzenepropanal (0.69), cinnamyl aldehyde (0.69), and benzaldehyde (0.70) were higher than CAL (0.63), which may cause a profound impact on an individual's health and well-being. Overall, the present study advances the understanding of the photodegradation processes and health impacts of fragrance ingredients. Environ Toxicol Chem 2021;40:2705-2714. © 2021 SETAC.

The aim of this study to evaluate the effect of Bacillus clausii biostimulation on the phenolic profile of black sesame sprouts. Sesame seeds were treated with three bacterial concentrations (103, 105, and 107 CFU/mL) and then germinated. The phenolic compounds in the seeds were quantified and identified using UPLC-DAD-MS. Interactions between B. clausii and sesame seed surface were analyzed through attachment analysis and molecular docking. B. clausii-mediated biostimulation at 103, 105, and 107 CFU/mL increased the phenolic content by 93%, 83%, and 56%, respectively. The attachment of B. clausii to the seeds was presented at a range of 6–18%. Biostimulation could be involved in the synthesis of β-coumaric acid hexoside I and luteolin C-deoxyhexoside C-hexoside I and the increase in the levels of cinnamic acid (41.11-fold), protocatechuic acid (1.5-fold), xanthoxylol malonyl trihexoside (2.13-fold), hydroxysesamolin trihexoside II (2.10-fold), sesaminol trihexoside I (1.10-fold), and sesaminol trihexoside II (1.12-fold), compared with control sprouts. Levels of gentisic acid (1.49-fold), apigenin (1.34-fold), apigenin C-pentoside C-hexoside I (1.50-fold), hydroxysesamolin trihexoside I (1.48-fold), and pinoresinol dihexoside I (7.43-fold) increased during biostimulation compared with the seed control. The concentration of gluconic acid, a non-phenolic compound, was found to be increased 1.39-fold. Results from molecular docking studies revealed that binding energies for surfactin binding with galacturonic acid and xylose were − 3.6 and − 3.3 kcal/mol, respectively. Thus, B. clausii-mediated biostimulation can be used to produce black sesame sprouts with high phenolic content and valuable phenolics to generate new sprout lines.

A bioassay-guided approach was employed to identify the active compounds from the whole herb of Spiranthes sinensis (Pers.) Ames, an orchidaceous medicinal plant. As a result, fourteen compounds were obtained from the active fractions. The structures of the isolates were identified as methyl 4-[2-(butoxymethyl)-5-formyl-pyrrol-1-yl] butyrate (1), 5,3′-dihydroxy-3,7,4′-trimethoxyflavone (2), populnin (3), scutellarein (4), quercetin (5), kaempferol (6), stigmasterol-3-O-β-D-glucopyranoside (7), β-daucosterol (8), trans-p-hydroxy cinnamic acid (9), 4-hydroxybenzoic acid methyl ester (10), 3-(4-tolyloxy)-propanoic acid (11), 2-benzothiazolol (12), ethyl ferulate (13) and kumatakenin (14) by comparing the spectroscopic data from the isolated compounds with the data reported in the literature. Compound 1 was a new natural compound. Compounds 2, 4–6 and 9–14 were first reported from the genus Spiranthes. Compound 7 was isolated from S. sinensis for the first time. In addition, compounds 5, 6, 11 and 13 were found to have potent anti-acetylcholinesterase (anti-AChE) activities with IC50 values ranging from 8.63 ± 0.37 to 19.97 ± 1.05 μg/mL, which indicates that S. sinensis has the potential in the development of new anti-Alzheimer’s disease (anti-AD) drugs.

Styrene is a food-borne toxicant in wheat beer and due to its classification as possibly carcinogenic to humans by the International Agency for Research on Cancer in 2002, mitigation strategies had to be developed. Aiming at understanding the impact of the barley to wheat malt ratio (grain bill) during mashing on the contents of soluble and free (i) cinnamic, (ii) p-coumaric, and (iii) ferulic acid, precursors of (i) styrene and the desired vinyl aromatics (ii) 4-vinylphenol and (iii) 2-methoxy-4-vinylphenol in wheat beer, wort was prepared at four different barley to wheat malt ratios of 100:0, 25:75, 50:50, and 0:100 (w/w). Additionally, the malts were produced at different germination temperatures and aeration rates (12/32, 18/35, 18/25, 24/18, and 26/25 (°C; L/min)) to consider these two further parameters as well. Thereby, soluble and free phenolic acid contents in wort showed linear correlations to the percentage of wheat in the grain bill, highlighting the absence of synergistic effects when mixing barley and wheat malts. In contrast, the results described the phenolic acid contents as a function of the concentrations in the respective barley and wheat wort, multiplied by their percentage in the grain bill. However, a clear recommendation for favorable barley to wheat malt ratios leading to a decrease of soluble and free cinnamic acid in wort could not be made, as the contents in the present study proved to be highly dependent on the barley and wheat varieties used during mashing and the parameters applied during malting. This was not the case for p-coumaric acid for which a clear decrease of the soluble and free forms was found with increasing wheat malt contents. Differently, the soluble form of ferulic acid increased with an increasing percentage of wheat malt, while the free form decreased. The malting parameters clearly recommended high germination temperatures and low aeration rates when aiming at a reduction of undesired cinnamic acid in wort. Fortunately, soluble and free p-coumaric and ferulic acid contents were only slightly affected, indicating that the formation of the characteristic wheat beer aroma might not suffer when applying these favorable conditions for styrene reduction.

The dessert bananas genotype are typically AA, AAA, and AAB, while ABB is classified as cooking bananas. Their nutritional content can be accessed much better than cooking bananas by the human body because they can be consumed directly without processing. This present study aimed to investigate the metabolite profiles of the ripe pulp of ten Indonesian dessert bananas cultivars represents the commercial interest and unpopular cultivars groups by UHPLC-Q-Orbitrap HRMS. They were Ambon Putih, Ambon Kuning, Ambon Badak, Ambon Lumut, Raja Sereh, Raja Bulu, Lampung, Papan, Rejang, and Udang. Nineteen metabolites were putatively identified in all of the cultivars studied. The main groups were fatty acids and the others catecholamine, quinone, phenol, flavonoid, cinnamic acid, organic acid, indole, and amino acid groups. Some of them were important bioactive compounds such as linolenic acid, palmitelaidic acid, linoleic acid, p-coumaric acid, dopamine, myricetin-deoxyhexose-hexoside, eugenol, 1,4-benzoquinone, and antroquinonol. The PCA score and loading plot showed the ten cultivars were separated into two groups based on linolenic acid as the first (PC1, 57%) and p-coumaric acid (PC2, 38%) as the second principal component with the 95% total variance explained. There was no relationship between PCA grouping and the genome group in terms of composition and metabolite content. These results provide valuable information for plant breeding programs, especially in banana biofortification for the future.

Cinnamomum bejolghota (Buch.-Ham.) Sweet is traditionally use as anthelmintic and cardiotonic agent. The objective of our current experiment is to establish the traditional claim by determining the in vitro anthelmintic and antihypertensive activity of extract and isolated compounds from the leaves of the plant. Isolation of compounds was carried out by bioassay guided method from hexane and ethanol extract. In vitro anti-hypertensive activity was carried out by angiotensin converting enzyme (ACE) inhibitory method. Anthelmintic activity was done by measuring the effect of isolated compounds on the survivability of adult nematode, egg hatching and larval development of Caenorhabditis elegans. From the plant, thirteen compounds (1-13) were characterized by using chromatography and spectroscopic methods and were tested for in vitro anthelmintic and ACE inhibitory activity. Compounds linalool (1), β-sitosterol (6), cinnamic acid (11), fridelin (12) exhibited promising ACE inhibitory activity with IC50 value of 99.02 ± 0.44, 65.87 ± 0.72, 45.36 ± 0.16 and 45.45 ± 2.31 μg/ml respectively. Further, geranial (4) exhibited the highest anthelmintic property when tested against adult C. elegans with an ED50 of 57.55 ± 4.47 µg/ml. Geranial treated eggs showed that at a concentration of 47.65 ± 1.917 µg/ml approximately 50% of the eggs did not hatch and at a concentration of 200 µg/ml compound was very effective in hindering the hatching of eggs (88.66 ± 0.67%). The larval development assay shows that at a concentration of 38.73 ± 2.57 µg/ml survival of about 50% of larvae was observed. To the best of our knowledge, this is the first report of isolation of anthelmintic and antihypertensive chemical moiety from C. bejolghota and can be developed into a novel phyto-pharmaceutical product.

Background: In Traditional Chinese Medicine (TCM), the heads and tails of Angelica sinensis (Oliv.) Diels (AS) is used in treating different diseases due to their different pharmaceutical efficacies. The underline mechanisms, however, have not been fully explored. Objective: Novel mechanisms responsible for the discrepant activities between AS heads and tails were explored by a combined strategy of transcriptomes and metabolomics. Method:: Six pairs of the heads and tails of AS roots were collected in Min County, China. Total RNA and metabolites, which were used for RNA-seq and untargeted metabolomics analysis, were respectively isolated from each AS sample (0.1 g) by Trizol and methanol reagent. Subsequently, differentially expressed genes (DEGs) and discrepant pharmaceutical metabolites were identified for comparing AS heads and tails. Key DEGs and metabolites were quantified by qRT-PCR and targeted metabolomics experiment. Results: Comprehensive analysis of transcriptomes and metabolomics results suggested that five KEGG pathways with significant differences included 57 DEGs. Especially, fourteen DEGs and six key metabolites were related to the metabolic regulation of Phenylpropanoid biosynthesis (PB) pathway. Results of RT-qPCR and targeted metabolomics indicated that higher levels of expression of crucial genes in PB pathway, such as PAL, CAD, COMT and peroxidase in the tail of AS, were positively correlated with levels of ferulic acid-related metabolites. The average content of ferulic acid in tails (569.58±162.39 nmol/g) was higher than those in the heads (168.73 ± 67.30 nmol/g) (P˂0.01); Caffeic acid in tails (3.82 ± 0.88 nmol/g) vs heads (1.37 ± 0.41 nmol/g) (P˂0.01), and Cinnamic acid in tails (0.24 ± 0.09 nmol/g) vs heads (0.14 ± 0.02 nmol/g) (P˂0.05). Conclusion: Our work demonstrated that overexpressed genes and accumulated metabolites derived from PB pathway might be responsible for the discrepant pharmaceutical efficacies between AS heads and tails.

Cinnamomum zeylanicum and Ocimum basilicum are two plants used by many cultures for food and medicinal purposes. The phenolic composition of ethanol extracts of both plants were determined by HPLC–DAD. A total of seventeen compounds were identified in C. zeylanicum with trans cinnamic acid (179.90 ± 0.45 µg/g) and coumarin (84.50 ± 0.41 µg/g) as major constituents while ten compounds were detected in O. basilicum with rosmarinic acid (360.40 ± 1.28 µg/g) and vanillic acid (36.30 ± 0.25 µg/g) as major constituents. C. zeylanicum exhibited higher inhibition on AChE (54.30 ± 0.97%) and BChE (66.43 ± 0.84%) than O. basilicum with lower AChE (23.43 ± 0.51%) and BChE (33.83 ± 0.75%) inhibitions. Both extracts showed moderate inhibition of tyrosinase and urease enzymes. The quorum sensing (QS) inhibition of O. basilicum and C. zeylanicum was evaluated by two assays: violacein inhibition on Chromobacterium violaceum CV12472 and QS inhibition on Chromobacterium violaceum CV026. Excellent inhibition of violacein synthesis in CV12472 was exhibited by C. zeylanicum with 100% inhibtion at MIC to MIC/4 and further inhibitions of 48.0 ± 2.0% (MIC.8) and 27.9 ± 1.2% (MIC/16). QS inhibition diameter zones on C. violaceum CV026 at MIC were 13.0 ± 1.0 mm and 10.5 ± 1.0 mm for C. zeylanicum and O. basilicum respectively. Since both extracts could inhibit violacein synthesis in CV12472 and QS in CV026, they could block signal production and signal reception in QS mediated processes in bacteria. These results indicate that both plants can be used to remedy microbial resistance and Alzheimer’s diseases.

A fast and simple ultra-high performance supercritical fluid chromatography method has been developed for the determination of six analytes, namely (paeonol, coumarin, cinnamic alcohol, cinnamic acid, paeoniflorin and amygdalin) in Guizhi Fuling capsule and tablet samples. The influence of the key chromatographic parameters for the separation purposes was evaluated. The optimal column was Trefoil CEL1 column. The optimal mobile phase was a gradient mixture of carbon dioxide and methanol at flow rate of 1.0 mL min-1 . The back pressure of the system was set to 1.38×107 Pa and the temperature to 45 ℃. The six compounds were separated within 11 min by the proposed ultra-high performance supercritical fluid chromatography method with satisfactory resolution. Method validation confirmed that the procedure is accurate with the recovery rates from 87.04% to 104.30%, intra-day precision values less than less than 4.81% and inter-day precision less than 5.22%, and linear with R2 higher than 0.9967. Therefore, this work provides a simple and novel method for the simultaneous analysis of six compounds in Guizhi Fuling capsule and tablet samples. This article is protected by copyright. All rights reserved.

The hybrid approach, encompassing two pharmacophores in one molecular scaffold, has attracted much attention in medicinal chemistry. In this study, we synthesized a panel of hybrid molecules based on the natural active ingredients, β-ionone and 3,4,5-trimethoxycinnamic acid. The results exhibited that 3,4,5-trimethoxy-hybrid displayed the most excellent cytotoxicity against cancer cells, whereas, the electron effect of substituents plays no distinct effect on antiproliferative activity. The cytotoxicity of 3,4,5-trimethoxy-hybrid may be due to its cell cycle arrest and apoptosis-inducing activities, which may be relationship with the reactive oxygen species generation, redox imbalance, lipid peroxidation and the collapse of mitochondrial membrane potential induced by 3,4,5-trimethoxy-hybrid in A549 (human lung adenocarcinoma) cells. In conclusion, 3,4,5-trimethoxy-hybrid could induce cancer cell apoptosis through the reactive oxygen species generation.

Cilj rada je prikazati sintezu i evaluaciju konjugata fenilboronične i cimetne kiseline. Fenilboronična kiselina pripada derivatima borne kiseline. Poznata je po svojim mogućim medicinskim svojstvima te je istraživana kao sredstvo u liječenje raka. Cimetna kiselina je široko zastupljena u biljnom svijetu, a izvor je većine derivata hidroksicimetne kiseline poput kumarinske, kafeinske, ferulinske i sinapinske kiseline. U ovom radu opisane su fenilboronična i cimetna kiselina općenito, njihova kemijska svojstva i strukture, upotreba njihovih derivata, te konačno sinteza fenilboronične i cimetne kiseline. Za potrebe rada korištena je relevantna literatura koja se odnosi na stručne članke i knjige koji su u skladu sa temom rada. The aim of this work is to present the synthesis and evaluation of the conjugate of phenylboronic acid and cinnamic acid. Phenylboronic acid belongs to the derivatives of boric acid. It is known for its potential medicinal properties and has been explored as a treatment for cancer. Cinnamic acid is widely distributed in the plant world and is the source of most hydroxycinnamic acid derivatives such as coumarin, caffeic acid, ferulic acid, and sinapic acid. In this paper, phenylboronic and cinnamic acids in general, their chemical properties and structures, the use of their derivatives and finally the synthesis of phenylboronic and cinnamic acids are described. Relevant literature was consulted for the paper, referring to technical articles and books corresponding to the subject of the paper.

Rak i malarija su smrtonosne bolesti koje predstavljaju značajan globalni javnozdravstveni problem. Učinkovitost postojećih citostatika i antimalarika opada uslijed pojave rezistencije, zbog čega je potrebno kontinuirano istraživati nove potencijalne lijekove. Popularan pristup u razvoju novih lijekova je molekulska hibridizacija, odnosno kovalentno povezivanje dva bioaktivna spoja s ciljem poboljšanja njihovog djelovanja. U okviru ovog doktorskog rada sintetizirani su hibridni spojevi harmina, -karbolinskog alkaloida s izraženim antimalarijskim i protutumorskim djelovanjem, i: 1) derivata cimetne kiseline (harmicini), 2) klorokina (harmikini), 3) ferocena (harmiceni). U pripravi harmicina korištena je bakrom(I) katalizirana azid-alkin cikloadicija, odnosno klik-reakcija koja je rezultirala harmicinima triazolskog tipa. Harmikini i harmiceni pripravljeni su korištenjem klik-reakcije te reakcije povezivanja amina i karboksilnih kiselina, dajući harmikine i harmicene triazolskog i amidnog tipa. Za potrebe klik-reakcija sintetizirani su odgovarajući alkini i azidi - karbolina, derivata cimetne kiseline, 7-klorkinolina te ferocena, dok su amini i karboksilna kiselina harmina te karboksilna kiselina i amini 7-klorkinolina pripravljeni za potrebe reakcija povezivanja. Novi spojevi karakterizirani su uobičajenim analitičkim i spektroskopskim metodama te je ispitano njihovo antiproliferativno i antimalarijsko djelovanje in vitro. U seriji harmicina najjače antiproliferativno djelovanje ostvarili su triazoli 49ae, dok su u seriji harmikina najcitotoksičniji bili triazoli 54 i 57. Najsnažnije antiproliferativno djelovanje među harmicenima prema svim ispitivanim staničnim linijama pokazao je amid 82, dok su harmiceni triazolskog tipa 67, odnosno 66 i 69 pokazali značajno i selektivno djelovanje prema MCF-7 i HCT116. Najbolje antimalarijsko djelovanje na eritrocitnu fazu životnog ciklusa svih ispitanih sojeva P. falciparum, u nanomolarnim koncentracijama, pokazali su harmikini. Spoj 63 ispoljio je 5,5 puta snažniji učinak u odnosu na klorokin (CQ) (IC50 = 2 ± 0,3 nM), dok je spoj 65 bio najučinkovitiji prema sojevima plazmodija rezistentnima na postojeće antimalarike. Temeljem dobivenih rezultata može se zaključiti da harmikini predstavljaju spojeve uzore za razvoj novih potencijalnih antimalarika, dok je harmicine i harmicene potrebno razvijati kao potencijalne protutumorske lijekove. Cancer and malaria are life-threatening diseases that pose a permanent public health problem. Existing cytostatic and antimalarial drugs are progressively losing their efficacy due to the development of drug resistance. Thus, there is a constant need for the development of novel and effective drugs. One of the possible approaches is molecular hybridization, i.e. covalent linking of two bioactive moieties into a single molecule with improved properties. In this dissertation, hybrids comprising harmin, a -carboline alkaloid with pronounced antimalarial and antitumor activity, and: 1) cinnamic acid derivatives (harmicines), 2) chloroquine (harmiquins), 3) ferrocene (harmicenes) were prepared. The harmicines were synthesized by a copper(I)-catalyzed azide-alkyne cycloaddition ("click" reaction) leading to triazole-type hybrids. On the other hand, harmiquins and harmicenes were prepared by both "click" and coupling reactions, giving triazole- and amide-type harmiquins and harmicenes. To obtain the required starting compounds for the "click" reaction, synthetic routes to -carboline-, cinnamic acid derivative-, 7-chloroquinoline-, and ferrocene-based alkynes and azides were developed. For the purpose of coupling reactions, 7-chloroquinoline- and harmine-based amines and acids were prepared. The novel compounds were characterized by standard methods (1H and 13C NMR, IR, MS). The antimalarial activity of the prepared compounds was evaluated in vitro against the erythrocytic and hepatic stages of the Plasmodium life cycle, as well as the antiproliferative activity against a panel of human tumor cell lines. Among the harmicines, triazoles 49a-e exhibited the strongest antiproliferative activity, whereas in the harmiquins series, triazoles 54 and 57 were the most cytotoxic compounds. Among the harmicenes, amide 82 showed the strongest cytotoxic activity against all tested cell lines (IC50 < 10 M), whereas triazole-type harmicenes 67, 66, and 69 displayed significant and selective activity against MCF-7 and HCT116. Harmiquins have shown the best antimalarial activity against the erythrocytic phase of chloroquine-sensitive and -resistant P. falciparum strains (IC50 in low nanomolar concentrations). Compound 63 showed a 5.5-fold stronger effect than chloroquine (IC50 = 2 ± 0.3 nM), while compound 65 was the most effective against resistant Plasmodium strains. The results suggest that harmiquins represent novel antimalarial hits, whereas further studies including harmicines and harmicenes should focus on their anticancer properties.

Cinamil alkohol in cimetova kislina sta naravni spojini, ki se uporabljata v parfumski in kozmetični industriji ter farmaciji. Najbolj znana je njuna prisotnost v cimetovcu, ki spada v družino lovorovk (Lauraceae). Cinamil alkohol in cimetova kislina sta sestavini eteričnega olja cimeta, ki ga pridobivajo iz listov, lubja in korenin. Pri standardnih pogojih je cinamil alkohol bela do rumenkasta kristalna trdna snov, s prijetnim, cvetličnim in sladkim vonjem ter okusom po cimetu. Cimetova kislina pa je bela kristalna organska spojina, katere vonj spominja na med. V naravi so cimetova kislina in njeni derivati zelo razširjeni, a jih večinoma najdemo v zelo nizkih koncentracijah. Sintezno pridobljena cimetova kislina pa nastaja s Perkinovo reakcijo. Namen diplomske naloge je bil sintetizirati derivate cinamil alkohola in cimetove kisline ter nastale produkte olfaktorno ovrednotiti. Uspešno smo sintetizirali deset njunih derivatov, po strukturi estrov in etrov. Ena reakcija ni potekla. Vse produkte smo očistili s kolonsko adsorpcijsko kromatografijo, kjer smo za razvijanje kromatogramov uporabili mobilno fazo, sestavljeno iz zmesi etilacetata in heksana v volumskem razmerju 1 : 4 ter 1 : 6. Uspešnost reakcij in identiteto produktov smo preverili z instrumentalnimi analiznimi metodami, in sicer z uporabo jedrske magnetne resonance ter infrardeče spektroskopije. Nato smo končne spojine olfaktorno vrednotili z vonjalnim testom, s katerim smo preverjali prijetnost in jakost vonjav ter asociacije na druge vonje. Večina derivatov cinamil alkohola in cimetove kisline ima prijeten vonj. Povprečna ocena jakosti vonjev testiranih vzorcev ima šibek do zmerno močan vonj. Vonji niso bili konstantni in so se tekom vonjalne analize spreminjali. Pri vrednotenju vzorcev so anketiranci označili cinamil butirat, cinamil fenilacetat in cinamil heksileter kot najprijetnejše vonjave. Pri opisovanju vonjav nismo ugotovili nobenih razlik med osebami, ki parfume uporabljajo in tistimi, ki jih ne. Cinnamyl alcohol and cinnamic acid are natural compounds used in the perfume, cosmetics and pharmaceutical industries. They are best known to be found in cinnamon tree, which belongs to the family of laurels (Lauraceae). Cinnamyl alcohol and cinnamic acid are components of cinnamon essential oil, which is extracted from the leaves, bark and roots of cinnamon. Under standard conditions, cinnamyl alcohol is a white to yellowish crystalline solid, with a pleasant, floral and sweet aroma and cinnamon taste. Cinnamic acid is a white crystalline organic compound with an odour reminiscent of honey. Cinnamic acid and its derivatives are widespread in nature, but are mostly found in very low concentrations. Synthetically produced cinnamic acid is produced by the Perkin reaction. The aim of the thesis was to synthesize derivatives of cinnamyl alcohol and cinnamic acid derivatives and and evaluate these products in an olfactory analysis. Ten of their derivatives were successfully synthesised, according to the structure of esters and ethers. One reaction did not proceed. All the products were cleaned by column adsorption chromatography, where chromatograms were developed using a mobile phase consisting of a mixture of ethyl acetate and hexane in volume ratios of 1 : 4 and 1 : 6. The success of the reactions and the identity of the products were verified by instrumental analytical methods, nuclear magnetic resonance and infrared spectroscopy. The final products were then evaluated olfactorially by an odour test, which was used to check the pleasantness and strength of aromas and their associations with other odours. Most derivatives of cinnamyl alcohol and cinnamic acid have a pleasant smell. The average odour strength rating of the tasted samples has a weak to moderately strong odour. The odours were not constant and varied during the odour analysis. When evaluating the samples, respondents indicated cinnamyl butyrate, cinnamyl phenylacetate and cinnamyl hexyl ether as the most pleasant odours. No differences were found between respondents who use perfumes and those who do not.

[ES] Los residuos de envases alimentarios contribuyen en gran medida a la actual crisis medioambiental provocada por los plásticos. Por ello, la industria alimentaria necesita soluciones de envasado más sostenibles y respetuosas con el medio ambiente, utilizando materiales biodegradables y activos para alargar la vida útil de los alimentos. En este sentido, la presente tesis doctoral tiene como objetivo la obtención de películas activas a base de almidón y PLA mediante la incorporación de ácidos ferúlico o cinámico como compuestos activos, con el fin de desarrollar laminados multicapa que cumplan con los requisitos de envasado de alimentos, con capacidad antibacteriana para alargar la vida útil del producto. La incorporación de los ácidos ferúlico y cinámico a las matrices de almidón de yuca mediante el proceso de mezclado en fundido, al 1 y 2%, promovió la plastificación de la película, probablemente debido a la hidrólisis parcial del polímero durante el proceso de mezclado. Los análisis de la actividad antibacteriana de las películas frente a Escherichia coli y Listeria innocua, en medio de cultivo, revelaron que las películas con ácido cinámico eran más eficaces para inhibir el crecimiento bacteriano, y que Listeria innocua era más sensible a ambos ácidos que E. coli. Cuando los ácidos se incorporaron a las matrices de PLA al 1 y 2% mediante mezclado en fundido, las propiedades funcionales de las películas no se vieron muy afectadas. Sin embargo, los ensayos antimicrobianos in vitro con L. innocua y E. coli, no mostraron acción antibacteriana. Los estudios de liberación mostraron una liberación muy limitada de los ácidos desde la matriz de PLA debido al estado vítreo de la matriz polimérica y a su naturaleza hidrofóbica, que limitan el hinchamiento y la relajación del polímero en contacto con medios acuosos, como muchas matrices alimentarias. Por lo tanto, para promover la liberación del compuesto activo desde la matriz de PLA, se analizaron diferentes estrategias: 1) plastificar las películas termoprocesadas con PEG 1000, 2) aumentar la concentración de los compuestos en la película, 3) procesar las películas por casting y 4) anclar los compuestos activos a la superficie de la película. Sólo la incorporación superficial de ferúlico o cinámico en las películas de PLA dio lugar a una inhibición significativa del crecimiento bacteriano. La pulverización de las películas de PLA con soluciones etanólicas de ácido permitió la formación superficial de una capa sobre concentrada de compuestos activos en las películas, con formaciones cristalinas que dio lugar a una adecuada liberación de activos para inhibir el crecimiento bacteriano. Disoluciones de PLA-ácido, utilizando mezclas de acetato de etilo con DMSO o ácido acético glacial, fueron electrodepositadas en la superficie de las películas. Los sistemas con DMSO produjeron fibras con una elevada superficie específica que inhibieron significativamente el crecimiento bacteriano, mientras que los sistemas con ácido acético produjeron estructuras particuladas sin actividad antimicrobiana. Se consideró la incorporación superficial de los compuestos activos para obtener películas de tres capas PLA/almidón/PLA (PSP) con mejores propiedades funcionales y capacidad antimicrobiana. Las películas cargadas superficialmente, tanto por electrospinning como por pulverización, mostraron una eficaz inhibición del crecimiento de E. coli y L. innocua, siendo las películas recubiertas por electrospinning más eficaces que las pulverizadas. Por lo tanto, los laminados PSP, con incorporación superficial de ácidos ferúlico o cinámico, representan una buena alternativa para obtener materiales de envasado de alimentos activos, con capacidad para preservar la calidad de los alimentos y prolongar su vida útil. No obstante, son necesarios más estudios sobre aplicaciones específicas en alimentos reales para determinar la posible aplicación industrial y la viabilidad económica de estos materiales., [CA] Els residus d' envasos alimentaris contribueixen en gran mesura a l' actual crisi mediambiental provocada pels plàstics. Per això, la indústria alimentària necessita solucions d' envasament més sostenibles i respectuoses amb el medi ambient, utilitzant materials biodegradables i actius per allargar la vida útil dels aliments. En aquest sentit, aquesta tesi doctoral té com a objectiu l' obtenció de pel·lícules actives a base de midó i PLA mitjançant la incorporació d' àcids ferúlic o cinàmic com a compostos actius, per tal de desenvolupar laminats multicapa que compleixin amb els requisits d' envasament d' aliments, amb capacitat antibacteriana per allargar la vida útil del producte. La incorporació dels àcids ferúlic i cinàmic a les matrius de midó de iuca mitjançant el procés de mesclament en fos, a l'1 i 2% p/p, va promoure la plastificació de la pel·lícula, probablement a causa de la hidròlisi parcial del polímer durant el procés de barret. Les anàlisis de l'activitat antibacteriana de les pel·lícules enfront d'Escherichia coli i Listeria innocua, en medi de cultiu, van revelar que les pel·lícules amb àcid cinàmic eren més eficaces per inhibir el creixement bacterià, i que Listeria innocua era més sensible a tots dos àcids que E. coli. Quan els àcids van incorporar a les matrius de PLA a l'1 i al 2% mitjançant mesclament en fos, les propietats funcionals de les pel·lícules no es van veure gaire afectades. No obstant això, els assajos antimicrobians in vitro amb L. innocua i E. coli, no van mostrar acció antibacteriana. Els estudis d'alliberament van mostrar un alliberament molt limitat dels àcids ferúlic i cinàmic des de la matriu de PLA a causa de l'estat vitri de la matriu polimèrica i a la seva naturalesa hidrofòbica, que limiten l'hinxament i la relaxació del polímer en contacte amb mitjans aquosos, com moltes matrius alimentàries. Per tant, per promoure l' alliberament del compost actiu des de la matriu de PLA, es van analitzar diferents estratègies: 1) plastificar les pel·lícules termoprocessades amb PEG 1000, 2) augmentar la concentració dels compostos a la pel·lícula, 3) processar les pel·lícules per casting i 4) ancorar els compostos actius a la superfície de la pel·lícula. Només la incorporació superficial de ferúlic o cinàmic a les pel·lícules de PLA va donar lloc a una inhibició significativa del creixement bacterià. La polvorització de les pel·lícules de PLA amb solucions etanòliques d'àcid va permetre la formació superficial d'una capa sobreconcentrada de compostos actius a les pel·lícules, amb formacions cristal·lines, que va donar lloc a un adequat alliberament d'actius per inhibir el creixement bacterià. Dissolucions de PLA-àcid, utilitzant mescles d'acetat d'etil amb DMSO o àcid acètic glacial, van ser electrodepositades a la superfície de les pel·lícules. Els sistemes amb DMSO van produir fibres amb una elevada superfície específica que van inhibir significativament el creixement bacterià, mentre que els sistemes amb àcid acètic van produir estructures particulades sense activitat antimicrobiana. Es va considerar la incorporació superficial dels compostos actius per obtenir pel·lícules de tres capes PLA/midó/PLA (PSP) amb millors propietats funcionals i capacitat antimicrobiana. Les pel·lícules carregades superficialment, tant per electrospinning com per polvorització, van mostrar una eficaç inhibició del creixement d'E. coli i L. innocua, sent les pel·lícules recobertes per electrospinning més eficaços que les polvoritzades. Per tant, els laminats PSP, amb incorporació superficial d'àcids ferúlic o cinàmic, representen una bona alternativa per obtenir materials d'envasat d'aliments actius, amb capacitat per preservar la qualitat dels aliments i prolongar la seva vida útil. No obstant això, calen més estudis sobre aplicacions específiques en aliments reals per determinar la possible aplicació industrial i la viabilitat econòmica d' aquests materials., [EN] Food packaging waste is a major contributor to the current environmental crisis caused by conventional plastic. Therefore, the food industry needs more sustainable environmentally friendly packaging solutions, such as using biodegradable and active materials to extend the food shelf-life. In this sense, the present doctoral thesis aims to obtain active films based on starch and PLA by incorporating ferulic or cinnamic acids as active compounds, in order to develop multilayer assemblies useful to meet food packaging requirements, with antibacterial capacity to extend the product shelf life. The incorporation of ferulic and cinnamic acids into cassava starch matrices through melt-blending process, at 1 and 2% w/w, promoted the film plasticization, probably due to the partial hydrolysis of polymer during the melt-blending process. The analyses of the antibacterial activity of the films against E. coli and Listeria innocua strains, in culture medium, revealed that films with cinnamic acid were more effective at inhibiting the bacterial growth, and that L. innocua was more sensitive to both acids than E. coli. When the acids were incorporated into PLA matrices at 1 and 2% w/w by melt blending, the functional properties of the films were not greatly affected. However, the in vitro antimicrobial tests with L. innocua and E. coli, did not show antibacterial action. Release studies showed very limited release of the ferulic and cinnamic acids from the PLA matrix due to the glassy state of polymer matrix and its hydrophobic nature that limits the polymer swelling and relaxation in contact with aqueous media, such as many food matrices. Therefore, in order to promote the release of active compound from the PLA matrix, different strategies were analysed: 1) plasticizing the thermoprocessed films with PEG 1000, 2) increasing the concentration of the compounds in the film, 3) processing the films by casting and 4) anchoring the active compounds to the film surface. Only the surface incorporation of ferulic or cinnamic on PLA films gave rise to significant bacterial growth inhibition. Pulverization of PLA films with ferulic or cinnamic acid ethanol solutions allows the formation of an overconcentrated layer of active compounds on the films with crystalline formations that led to an adequate release of actives to inhibit the bacterial growth. PLA-acid solutions, using blends of ethyl acetate with dimethyl sulfoxide (DMSO) or glacial acetic acid, were electrospun on the film surface. DMSO systems produced fibre-structured mats with high specific surface that significantly inhibited bacterial growth, whereas acetic acid systems produce bead-based mats that not had antimicrobial activity. The surface incorporation of the active compounds was considered for obtaining three-layered films PLA/starch/PLA (PSP) with improved functional properties and antimicrobial capacity. Superficially loaded films by both electrospinning or pulverisation, showed effective growth inhibition of E. coli and L. innocua, electrospun films being more effective than pulverised, suggesting greater ability to release the active compounds. Therefore, PSP laminates, with surface incorporation of ferulic or cinnamic acids, represent a good alternative to obtain active food packaging materials with the capacity to preserve food quality and extend shelf life. Nonetheless, further studies on the material stability and specific applications in real foods are necessary to determine the possible industrial application and economic viability of these materials., The authors thank the Agencia Estatal de Investigación (Ministerio de Ciencia e Innovación, Spain) for the financial support through projects AGL2016-76699-R and PID2019-105207RB-I00.

This study was designed to investigate the phenolic acid contents and antioxidant activities of 14 clones of mint species (M. spicata, M. piperita, M. villoso nervata and M. dumetorum) that cultivated in Turkey. The phenolic acid contents were analysed using HPLC. The antioxidant activities of these Mentha species were evaluated by free radical scavenging activity (DDPH•), cation radical scavenging activity (ABTS•+) and reducing power activity tests. Additionally, total phenolic content of mint species was determined spectrophoto metrically using Folin-Ciacelteau’s reagent. Phenolic acid contents of Mentha were evaluated in two subclasses: benzoic acid and cinnamic acid derivatives. The rosmarinic acid (which is cinnamic acid derivative) was the main phenolic acid for all tested plant material changing from 5482.6 to 31982.7 mg/kg dry weight concentrations. p-hydroxy benzoic acid (ranging from 30.5 to 236.4 mg/kg dry weight) and syringic acid (ranging from 95.4 to 375.2 mg/kg dry weight) were most abundant benzoic acids derivatives found in tested mint clones. According to DDPH● and ABTS●+ test results, while M. villoso nervata clone (originated from Osmaniye) has higher activity, M. spicata clone (originated from Manisa) has lower activity among the other clones. Reducing power activity of M. villoso nervata clone (originated from Osmaniye) was highest and M. spicata clone (originated from Konya) was lowest. It has been observed that the correlation between phenolic acid derivatives and antioxidant activity varied depending on used antioxidant activity methods. These results show that best Mentha for human health in terms of both phenolic acid content and antioxidant activity are the 3rd clone (M. spicata) and the 10th clone (M. villoso nervata) genotypes., Bu çalışma, Türkiye'de yetiştirilen M. spicata, M. piperita, M. villoso nervata ve M. dumetorum türlerine ait 14 nane klonlarının fenolik asit içerikleri ve antioksidan aktivitelerini araştırmak için tasarlanmıştır. Fenolik asit içerikleri HPLC kullanılarak analiz edilmiştir. Mentha türlerinin antioksidan aktiviteleri, serbest radikal giderme aktivitesi (DDPH•), katyon radikal giderme aktivitesi (ABTS• +) ve indirgeme gücü aktivite testleri ile değerlendirilmiştir. Ek olarak, nane türlerinin toplam fenolik içeriği, Folin-Ciacelteau’nun reaktifi kullanılarak spektrofotometrik olarak belirlenmiştir. Nane türlerinin fenolik asit içerikleri benzoik ve sinamik asit türevi olmak üzere iki alt sınıfta değerlendirilmiştir. Rosmarinik asit (sinnamik asit türevi) konsantrasyonu, test edilen tüm bitki materyalleri için 5482.6'dan 31982.7 mg/kg kuru ağırlık arasında değişen ana fenolik asit olarak gözlemlenmiştir. p-hidroksi benzoik asit (30.5 ile 236.4 mg/kg kuru ağırlık arasında) ve şiringik asit (95.4 ile 375.2 mg/kg kuru ağırlık arasında), test edilen nane klonlarında en yüksek miktarda bulunan benzoik asit türevleridir. DDPH● ve ABTS●+ test sonuçlarına göre M. villoso nervata türü (Osmaniye kaynaklı klonu) daha yüksek aktiviteye sahipken, M. spicata türü (Manisa kaynaklı klonu) diğer klonlar arasında daha düşük aktiviteye sahip olduğu görülmüştür. M. villoso nervata türü (Osmaniye kaynaklı klonu) indirgeme gücü aktivitesi düşük iken en yüksek aktiviteyi M. spicata türü (Konya kaynaklı klonu) göstermiştir. Fenolik asit türevleri ile antioksidan aktivite arasındaki ilişkinin, kullanılan antioksidan aktivite yöntemlerine bağlı olarak değiştiği görülmüştür. Elde edilen sonuçlara göre hem fenolik asit içeriği hem de antioksidan aktivite açısından insan sağlığı için en yararlı nane türünün 3. klon (M. spicata) ve 10. klon (M. villoso nervata) genotipleri olduğunu tespit edilmiştir.

Amberlyst 15 resin supported the tandem reaction of cinnamic acids with phenols under solvent-free reaction condition has been introduced to afford 4-aryl-3,4-dihydrocoumarin (neoflavanone) derivat...

Divya-Swasari-Vati is a calcium containing polyherbal ayurvedic medicine prescribed for the lung-related ailments observed in the current pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 infections. The formulation is a unique quintessential blend of nine herbs cited in Ayurvedic texts for chronic cough and lung infection. Analytical standardization of herbal medicines is the pressing need of the hour to ascertain the quality compliance. This persuaded us to develop a simple, rapid, and selective high-performance thin-layer chromatographic method for Divya-Swasari-Vati quality standardization. The developed method was validated for the quantification of marker components, gallic acid, cinnamic acid, piperine, eugenol and glycyrrhizin, against reference standards in five different batches of Divya-Swasari-Vati. The analytes were identified by visualization at 254 nm, and by matching their retention factor with authentic standards. The developed method was validated as per the guidelines recommended by the International Council for Harmonization for parameters like, linearity, limit of detection, limit of quantification, accuracy, and precision. Therefore, the developed novel high-performance thin-layer chromatographic process could be employed for rapid standardization of Divya-Swasari-Vati and other related herbal formulation, which would aid in quality manufacturing and product development.

Necrotizing enterocolitis is characterized by an inflammatory condition in the intestine that could result in intestinal necrosis and cell death. Cinnamic acid, an unsaturated carboxylic acid, possesses anti-inflammatory capacity. However, the regulatory role of cinnamic acid on necrotizing enterocolitis has not been investigated yet. To this end, human fetal colon cells were incubated with increasing concentrations of lipopolysaccharides to establish a necrotizing enterocolitis cell model. Data from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis showed that lipopolysaccharides, in a dosage-dependent manner, reduced cell viability of fetal human colon cells. Also, cinnamic acid prevented the cytotoxic effect of lipopolysaccharides on fetal human colon cells and increased the cell viability. Furthermore, cinnamic acid attenuated lipopolysaccharides-induced decrease in interleukin-10 and increase in interleukin-6 and tumor necrosis factor-α caused by lipopolysaccharides. The lipopolysaccharides-induced increase in cell apoptosis in fetal human colon cells was accompanied with upregulated B-cell lymphoma 2 protein-associated X protein and downregulated B-cell lymphoma 2 protein. These changes were reversed by cinnamic acid treatment. Lastly, expression of protein for suppressor of cytokine signaling 3 was reduced, while phosphorylation of Janus kinase 2 and signal transducers and activators of transcription 3 were enhanced in lipopolysaccharides-induced fetal human colon cells. Once again, cinnamic acid reversed the expression of suppressor of cytokine signaling 3, phospho- Janus kinase 2, and phospho-signal transducers and activators of transcription 3 in lipopolysaccharides-induced fetal human colon cells. In conclusion, cinnamic acid exerted antiapoptotic and anti-inflammatory effects and protected enterocytes against necrotizing enterocolitis through regulation of signal transducers and activators of transcription-mediated Janus kinase 2/signal transducers and activators of transcription 3 pathway.

The related structure–activity relationships of cinnamic acid and its derivates have not been studied in details yet. Herein, antityrosinase and antioxidant activities of 18 compounds were evaluated. The results demonstrated that the substituents on the phenyl ring of cinnamic acid led to the enhancement of the inhibition on monophenolase and the weakening of the inhibition on diphenolase. Among these tested compounds, 9 was first discovered as a tyrosinase inhibitor in a reversible competitive manner with IC50 value of 68.6 ± 4.2 µm. Docking results demonstrated 9 located into the catalytic center of tyrosinase. Antioxidant assay indicated that only 1 hydroxyl group on the phenyl ring was not enough to possess the radical scavenging activity, and the number of hydroxyl groups may be more important. This study will be helpful in the development of new cinnamic acid derivates as tyrosinase inhibitors and antioxidants with higher efficacy.