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Anthocyanins are water-soluble naturally occurring flavonoids present in fruits, flowers, leaves, and roots of fruit plants and vegetables. One of the important anthocyanidin components of red wine and berries is delphinidin (DP). This review provides an update on the potential of DP in cancer therapy, with a further understanding of the mechanisms involved. Delphinidin has been shown to elicit inhibitory effects on catabolizing enzymes of human granulocytes and parasites, TNF-induced COX-2 expression in mouse epidermal cells, and reduce oxidative stress. It also inhibited anchorage-independent growth and caused cell death in breast cancer cell lines. Delphinidin increased Nrf2 expression, increased HO-1 production, and promoted mRNA expression of mitochondrial biogenesis-related factors. Further, DP has anti-proliferative and pro-apoptotic effects in various cancer cell lines such as lung, breast, and ovarian cancer cells. The mTOR-related pathway is the most important signaling pathway in the activation of autophagy, and DP has been shown to exert its cytotoxic effects on cancer cell lines via activating protein kinases. Among DP derivatives, delphinidin-3-O-glucoside has the best anticancer activity because it is easily absorbed. However, the metabolism of DP and its bioavailability in biological systems need to be explored to fully understand its benefits. [ABSTRACT FROM AUTHOR]

Permethylated anigopreissin A (PAA), a fully protected form of the natural anigopreissin A, was found in our previous study to be active against several cancer cells, up to IC50 0.24 μM for HepG2 cells. Herein, a total of thirteen PAA analogues with variations in the number, position of substituents and unsaturation were synthesised starting from a common precursor, and their ability to induce cell growth inhibition was tested. By comparing the antiproliferative effect of the analogues with PAA and with the help of computational studies, we have gained valuable insights into both the biological activity and structure of this natural class of compounds. Indeed, we discovered the importance of the C-3 ring in modulating the biological activity of PAA, as well as the crucial role of the trans configuration of the styryl double bond and the significance of substitutions on the other parts of the molecule.

Permethylated anigopreissin A (PAA), a fully protected form of the natural anigopreissin A, was found in our previous study to be active against several cancer cells, up to IC50 0.24 μM for HepG2 cells. Herein, a total of thirteen PAA analogues with variations in the number, position of substituents and unsaturation were synthesised starting from a common precursor, and their ability to induce cell growth inhibition was tested. By comparing the antiproliferative effect of the analogues with PAA and with the help of computational studies, we have gained valuable insights into both the biological activity and structure of this natural class of compounds. Indeed, we discovered the importance of the C-3 ring in modulating the biological activity of PAA, as well as the crucial role of the trans configuration of the styryl double bond and the significance of substitutions on the other parts of the molecule. [ABSTRACT FROM AUTHOR]

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The purple carrot cultivar 'Purple Sun' (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12–14, 16, 17, 19, 22, and 23), anthocyanins (3–5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (−) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, 'Purple Sun' is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations. [ABSTRACT FROM AUTHOR]

Newly synthesized 7-chloro-4-aminoquinoline–benzimidazole hybrids were characterized by NMR and elemental analysis. Compounds were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts) and carcinoma (HeLa and CaCo-2), leukemia, and lymphoma (Hut78, THP-1, and HL-60) cell lines. The obtained results, expressed as the concentration at which 50% inhibition of cell growth is achieved (IC50 value), show that the tested compounds affect cell growth differently depending on the cell line and the applied dose (IC50 ranged from 0.2 to >100 µM). Also, the antiplasmodial activity of these hybrids was evaluated against two P. falciparum strains (Pf3D7 and PfDd2). The tested compounds showed potent antiplasmodial activity, against both strains, at nanomolar concentrations. Quantitative structure–activity relationship (QSAR) analysis resulted in predictive models for antiplasmodial activity against the 3D7 strain (R2 = 0.886; Rext2 = 0.937; F = 41.589) and Dd2 strain (R2 = 0.859; Rext2 = 0.878; F = 32.525) of P. falciparum. QSAR models identified the structural features of these favorable effects on antiplasmodial activities. [ABSTRACT FROM AUTHOR]

In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer), and SH-SY5Y (neuroblastoma) as well as on human embryonal lung fibroblast cell line MRC-5, which served as a reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. [ABSTRACT FROM AUTHOR]

Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide–alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges. [ABSTRACT FROM AUTHOR]

The persistence of human papillomavirus affects the processes of proliferation and differentiation of the stratified squamous epithelium of the cervix with the development of cervical intraepithelial neoplasia and cervical cancer. Hormonal factors have an impact on the process of neoplastic transformation. The aim of this study was an evaluation of the effect of glycyrrhizic acid on the viability of HeLa cervical adenocarcinoma cells at different concentrations of sex steroid hormones. The half-maximal inhibitory concentration (IC50) of glycyrrhizic acid against HeLa cervical adenocarcinoma cells was 72.2 μM. The IC50 of glycyrrhizic acid increased by 13.4% and 17% for testosterone, decreased by 1.8% and 11.8% for estradiol, and increased by 8.7% and 8.6% for progesterone, respectively, in the presence of the hormones at concentrations of 10 μM and 1 μM. Thus, testosterone and progesterone at concentrations of 10 and 1 μM diminished the antiproliferative effect of glycyrrhizic acid, while estradiol at a low concentration (1 μM) enhanced it. [ABSTRACT FROM AUTHOR]

Unlike MCF-7 cells, MDA-MB-231 cells are unresponsive to hormone therapy and often show resistance to chemotherapy and radiotherapy. Here, the antiproliferative effect of biocompatible montmorillonite (Mt) nanosheets on MDA-MB-231 and MCF-7 human breast cancer cells was evaluated by MTT assay, flow cytometry, and qRT-PCR. The results showed that the Mt IC50 for MDA-MB-231 and MCF-7 cells in a fetal bovine serum (FBS)-free medium was ~50 and ~200 µg/mL, and in 10% FBS medium ~400 and ~2000 µg/mL, respectively. Mt caused apoptosis in both cells by regulating related genes including Cas-3, P53, and P62 in MDA-MB-231 cells and Bcl-2, Cas-8, Cas-9, P53, and P62 in MCF-7 cells. Also, Mt arrested MCF-7 cells in the G0/G1 phase by altering Cyclin-D1 and P21 expression, and caused sub-G1 arrest and necrosis in both cells, possibly through damaging the mitochondria. However, fewer gene expression changes and more sub-G1 arrest and necrosis were observed in MDA-MB-231 cells, confirming the higher vulnerability of MDA-MB-231 cells to Mt. Furthermore, MDA-MB-231 cells appeared to be much more vulnerable to Mt compared to other cell types, including normal lung fibroblast (MRC-5), colon cancer (HT-29), and liver cancer (HepG2) cells. The higher vulnerability of MDA-MB-231 cells to Mt was inferred to be due to their higher proliferation rate. Notably, Mt cytotoxicity was highly dependent on both the Mt concentration and serum level, which favors Mt for the local treatment of MDA-MB-231 cells. Based on these results, Mt can be considered as an antiproliferative nanoagent against MDA-MB-231 cells and may be useful in the development of local nanoparticle-based therapies. [ABSTRACT FROM AUTHOR]

Introduction/Justification: Closely related to high UV exposure and comprising basal cell carcinoma, squamous cell carcinoma (SCC), and melanoma, skin cancer is the most prevalent tumor in the world. Cisplatin has been used for treatment of patients with skin squamous cell carcinoma (SSCC) with low response rate and pronounced adverse effects. Thus, the search for new chemotherapeutic agents for patients with SSCC or melanoma is required, and gold complexes have been explored as potential anticancer drugs. Targeting thioredoxin reductase or thiol-rich proteins, many gold complexes can induce cell death by reactive oxygen species. Objectives: Our study aimed to evaluate the in vitro anti-proliferative effects of a gold(I) complex with triphenylphosphine and 4-dimethylaminopyridine as ligand. Materials and Methods: The gold (I) complex was synthesized at the Department of Inorganic Chemistry, Institute of Chemistry, University of Campinas. Melanoma (UACC-62), squamous cell carcinoma of tongue (SCC4 and SCC15), and a non-tumoral cell line (HaCat, immortalized keratinocyte) were grown in complete medium [RPMI-1640 (Gilco®) supplemented with 5% fetal bovine serum (Gilco®) and 1% penicillin:streptomycin mixture (1000 U/mL:1000 µg/mL, Vitrocell, Brasil)] at 37 °C and 5% CO2. Each cell line (100 μL/well, in 96-well plates, 4 - 6 x10^4 cel/ml) was exposed to the gold (I) complex (100 μL/well, 0.25 to 250 µg/mL, in triplicate) and incubated for 48 h. Doxorubicin (100 μL/well, 0.025 to 25 µg/mL, in triplicate) was used as a positive control. Before (T0) and after (T1) sample addition, cells were fixed with 50% trichloroacetic acid (TCA, 50 μL/well), and cell viability was determined using the sulforhodamine B protocol at 540 nm with a microplate reader spectrophotometer (VersaMax, Molecular Devices). The difference between T0 and T1 absorbance values represented 100% of cell growth, and the proliferation (%) of each cell line in the presence of each sample concentration was calculated accordingly. Effective concentration representing the sample concentration required to promote 50% growth inhibition (GI50) for each cell line was calculated by sigmoidal regression using Origin 8.0 software. Results: The gold(I) complex showed potent anti-proliferative effect against UACC-62 cells (GI50 < 0.25 µg mL-1) being less active against SCC15 (GI50 ≈ 2.5 µg mL-1) and SCC4 (GI50: 10.2 µg mL-1) cells. Moreover, the anti-proliferative effect of gold(I) complex showed a good selectivity being almost 10x less active against HaCaT cells (GI50 ≈ 2.5 µg mL-1) in comparison to melanoma cells. Conclusion: This data indicated gold(I) complex with triphenylphosphine and 4-dimethylaminopyridine as ligands as a promisor candidate for treatment of patients with melanoma. Further in vitro and in vivo evaluations is required to evaluate the mechanism of action and toxicity of the complex. Acknowledgements: The study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio ao Ensino e à Pesquisa do Estado de São Paulo (FAPESP #2016/07729-4; #2023/09738-4; Cancer Theranostics Innovation Center, (CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375).

Aim: As far as is known, the pharmaceutical effects of neem on human B-lymphoblastoid (TK6) cells have not been studied until now. Hence, the present study aimed to obtain neem phenolic extracts for inhibits the proliferation of TK6 cells and explore some possible underlying mechanisms involved in these effects. Methods: Hexane extract (HE) was obtained in the first step. After that, the residual hexane was removed from the neem. The dried neem sample was used in a new extraction for obtaining the ethyl acetate extract (EAE). Total phenolic compounds (TPC) and total flavonoid contents (TFC) were determined by spectrophotometric methods. Lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to evaluate the cytotoxicity in TK6 cells. The stop at G0/G1 cell cycle and inducing apoptosis in the TK6 cells were analyzed by flow cytometry. For deoxyribonucleic acid (DNA) damage evaluation, the alkaline comet test was used. Results: The higher TFC (65.50 mg/g of extract ± 1.17 mg/g of extract) and TPC (52.08 mg of extract ± 0.88 mg of extract) were obtained in EAE compared to HE that was obtained TFC of 14.61 mg/g of extract ± 0.60 mg/g of extract and TPC of 3.20 mg/g of extract ± 1.20 mg/g of extract. EAE was more significantly cytotoxic to TK6 cells than HE. The apoptosis induction was higher after exposure to 15.0 µg/mL of EAE (11.29%) in comparison to 15.0 µg/mL of HE (2.52%). The G0/G1 phase increased from 72% negative control (NC) to 83% after treatment with neem extracts (15 µg/mL). Neem extracts were also able to cause DNA strand breaks in TK6 cells. Conclusions: The extraction residue from neem leaf after hexane extraction is a source important of cytotoxic and genotoxic molecules against TK6 cells, the results also can suggest that the toxic effects in TK6 cells can be provided most likely due to the presence of high content of TPC from neem extracts.

Globularia alypum L. (GA) belonging to the Globulariaceae family is a Mediterranean plant which is widely used in traditional Tunisian medicine. The aim of this study was to investigate the phytochemical composition, antioxidant, anti-arthritic, antiproliferative, antibacterial and antibiofilm potential of aqueous GA leaf extracts (AGAL). Quantitative analyses of the different constituents of extracts were evaluated by high-performance liquid chromatography with photodiode-array detection (HPLC-DAD). Spectrophotometric methods and chemical tests were used for antioxidant and anti-arthritic activities. The antiproliferative study was evaluated using colorectal cancer SW620 cells, while the antibacterial assessment and analysis of the antibiofilm effects were determined by the microdilution method and the crystal violet assay, respectively. AGAL extracts presented several components, mainly Nepetin-7-Glucoside and trans-ferrulic acid. The results showed that they had an important antioxidant (IC50 = 0.34; 0.38 and 1.20 mg/mL) and anti-arthritic (IC50 = 2.94 mg/mL) properties, and these effects are displayed in a dose-dependent manner. In addition, this extract demonstrated significant antiproliferative (IC50 = 50 µg/mL), antibacterial (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties especially against S. aureus. The results achieved confirm the important role of this plant as a source of therapeutic activities. [ABSTRACT FROM AUTHOR]

The essential oil from Conyza bonariensis (Asteraceae) aerial parts (CBEO) was extracted by hydrodistillation in a Clevenger-type apparatus and was characterized by gas chromatography–mass spectrometry. The antitumor potential was evaluated against human tumor cell lines (melanoma, cervical, colorectal, and leukemias), as well as non-tumor keratinocyte lines using the MTT assay. The effect of CBEO on the production of Reactive Oxygen Species (ROS) was evaluated by DCFH-DA assay, and a protection assay using the antioxidant N-acetyl-L-cysteine (NAC) was also performed. Moreover, the CBEO toxicity in the zebrafish model was assessed. The majority of the CBEO compound was (Z)-2-lachnophyllum ester (57.24%). The CBEO exhibited selectivity towards SK-MEL-28 melanoma cells (half maximal inhibitory concentration, IC50 = 18.65 ± 1.16 µg/mL), and induced a significant increase in ROS production. In addition, the CBEO's cytotoxicity against SK-MEL-28 cells was reduced after pretreatment with NAC. Furthermore, after 96 h of exposure, 1.5 µg/mL CBEO induced death of all zebrafish embryos. Non-lethal effects were observed after exposure to 0.50–1.25 µg/mL CBEO. Additionally, significant alterations in the activity of enzymes associated with oxidative stress in zebrafish larvae were observed. These results provide evidence that CBEO has a significant in vitro antimelanoma effect by increasing ROS production and moderate embryotoxicity in zebrafish. [ABSTRACT FROM AUTHOR]

The newly synthesized quinoline–benzimidazole hybrids containing two types of triazole-methyl-phenoxy linkers were characterized via NMR and elemental analysis. Additional derivatization was achieved by introducing bromine at the C-2 position of the phenoxy core. These novel hybrids were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts), leukemia and lymphoma cell lines: Hut78, THP-1 and HL-60, and carcinoma cell lines: HeLa and CaCo-2. The results obtained, presented as the concentration that achieves 50% inhibition of cell growth (IC50 value), show that the compounds tested affect tumor cell growth differently depending on the cell line and the dose applied (IC50 ranged from 0.2 to >100 µM). The quinoline–benzimidazole hybrids tested, including 7-chloro-4-(4-{[4-(5-methoxy-1H-1,3-benzo[d]imidazol-2-yl)phenoxy]methyl}-1H-1,2,3-triazol-1-yl)quinoline 9c, 2-(3-bromo-4-{[1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 10e, 2-{4-[(1-{2-[(7-chloroquinolin-4-yl)amino]ethyl}-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 14e and 2-{3-bromo-4-[(1-{2-[(7-chloroquinolin-4-yl)amino]ethyl}-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 15e, arrested the cell cycle of lymphoma (HuT78) cells. The calculated ADMET properties showed that the synthesized compounds violated at most two of Lipinski's rules, making them potential drug candidates, but mainly for parenteral use due to low gastrointestinal absorption. The quinoline–benzimidazole hybrid 14e, which was shown to be a potent and selective inhibitor of lymphoma cell line growth, obtained the highest binding energy (−140.44 kcal/mol), by docking to the TAO2 kinase domain (PDB: 2GCD). [ABSTRACT FROM AUTHOR]

Numerous studies have reported the pharmacological effects exhibited by Dittrichia viscosa, (D. viscosa) including antioxidant, cytotoxic, antiproliferative, and anticancer properties. In our research, our primary objective was to validate a prescreening methodology aimed at identifying the fraction that demonstrates the most potent antiproliferative and anticancer effects. Specifically, we investigated the impact of various extract fractions on the cytoskeleton using a screening method involving transgenic plants. Tumors are inherently heterogeneous, and the components of the cytoskeleton, particularly tubulin, are considered a strategic target for antitumor agents. To take heterogeneity into account, we used different lines of colorectal cancer, specifically one of the most common cancers regardless of gender. In patients with metastasis, the effectiveness of chemotherapy has been limited by severe side effects and by the development of resistance. Additional therapies and antiproliferative molecules are therefore needed. In our study, we used colon-like cell lines characterized by the expression of gastrointestinal differentiation markers (such as the HT-29 cell line) and undifferentiated cell lines showing the positive regulation of epithelial–mesenchymal transition and TGFβ signatures (such as the DLD-1, SW480, and SW620 cell lines). We showed that all three of the D. viscosa extract fractions have an antiproliferative effect but the pre-screening on transgenic plants anticipated that the methanolic fraction may be the most promising, targeting the cytoskeleton specifically and possibly resulting in fewer side effects. Here, we show that the preliminary use of screening in transgenic plants expressing subcellular markers can significantly reduce costs and focus the advanced characterization only on the most promising therapeutic molecules. [ABSTRACT FROM AUTHOR]

Cotinus coggygria Scop. is a valuable medicinal plant species with pronounced pharmacological potential due to its numerous biological activities. The herb is characterized by a high content of polyphenols among which is fustin. The anticancer activities of fustin, however, are extremely weakly studied. The aim of the present study was to investigate the in vitro antiproliferative potential of fustin isolated from the heartwood of C. coggygria against cell lines originating from two of the most common cancer types – breast (MDA-MB-231 and MCF7), and colon cancer (Colon 26).

Newly synthesized 7-chloro-4-aminoquinoline–benzimidazole hybrids were characterized by NMR and elemental analysis. Compounds were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts) and carcinoma (HeLa and CaCo-2), leukemia, and lymphoma (Hut78, THP-1, and HL-60) cell lines. The obtained results, expressed as the concentration at which 50% inhibition of cell growth is achieved (IC50 value), show that the tested compounds affect cell growth differently depending on the cell line and the applied dose (IC50 ranged from 0.2 to >100 µM). Also, the antiplasmodial activity of these hybrids was evaluated against two P. falciparum strains (Pf3D7 and PfDd2). The tested compounds showed potent antiplasmodial activity, against both strains, at nanomolar concentrations. Quantitative structure–activity relationship (QSAR) analysis resulted in predictive models for antiplasmodial activity against the 3D7 strain (R2 = 0.886; Rext2 = 0.937; F = 41.589) and Dd2 strain (R2 = 0.859; Rext2 = 0.878; F = 32.525) of P. falciparum. QSAR models identified the structural features of these favorable effects on antiplasmodial activities.

Four diastereomers of 16-azidomethyl substituted 3-O-benzyl estradiol (1–4) and their two estrone analogs (16AABE and 16BABE) were tested for their antiproliferative properties against human gynecological cancer cell lines. The estrones were selected for additional experiments based on their outstanding cell growth-inhibiting activities. Both compounds increased hypodiploid populations of breast cancer cells, and 16AABE elicited cell cycle disturbance as evidenced by flow cytometry. The two analogs substantially increased the rate of tubulin polymerization in vitro. 16AABE and 16BABE inhibited breast cancer cells' migration and invasive ability, as evidenced by wound healing and Boyden chamber assays. Since both estrone analogs exerted remarkable estrogenic activities, as documented by a luciferase reporter gene assay, they can be considered as promising drug candidates for hormone-independent malignancies. [ABSTRACT FROM AUTHOR]

Arabinoxylan has prebiotic properties, as it is able to resist digestion in the small intestine and undergoes fermentation in the large intestine. In this work, arabinoxylan was extracted from corn fiber using an alkaline solution and further purified with membrane processing. It was found that the extracts were mainly composed of xylose (50–52%), arabinose (37–39%), galactose (9%) and glucose (1–4%), with an A/X ratio of 0.72–0.77. All the extracts were composed of phenolic compounds, including ferulic acid derivatives such as dimers, trimers and tetramers. The purified extract had a lower concentration of ferulic and p-coumaric acid (0.004 and 0.02 mg/mgdry_weight, respectively) when compared to raw extract (19.30 and 2.74 mg/mgdry_weight, respectively). The same effect was observed for the antioxidant activity, with purified extracts having a lower value (0.17 ± 0.02 µmol TEAC/mg) when compared to the raw extract (2.20 ± 0.35 µmol TEAC/mg). The purified extract showed a greater antiproliferative effect against the HT29 cell line with EC50 = 0.12 ± 0.02 mg/mL when compared to the raw extract (EC50 = 5.60 ± 1.6 mg/mL). Both raw and purified extracts did not show any cytotoxicity to the Caco-2 cell line in the maximum concentration tested (10 mg/mL). [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most lethal and fourth most commonly diagnosed cancer worldwide. Sinapic acid, a derivative of hydroxycinnamic acid, is a promising phytochemical exhibiting numerous pharmacological activities in various systems. It is a substantial chain-breaking antioxidant that operates as a radical scavenger. The aim of this research was to investigate the antiproliferative effect of sinapic acid on the HT-29 cell line besides the mechanisms underlying this activity. The effect of sinapic acid on the viability of HT-29 cell line was investigated using XTT assay. The levels of BCL-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG were measured using ELISA. Gamma-H2AX and cytochrome c expressions were assessed semiquantitatively using immunofluorescence staining. Sinapic acid at 200 µm and higher doses produced a significant antiproliferative effect on HT-29 cells. The IC50 value was found to be 317.5 µm for 24 h. Sinapic acid (317.5 µm) significantly elevated cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG levels. The levels of gamma-H2AX foci are significantly higher, while the levels of cytochrome c are lower in sinapic acid-treated HT-29 cells. These results indicate that sinapic acid has antiproliferative, apoptotic, and genotoxic effects on colon cancer cells. [ABSTRACT FROM AUTHOR]

AbstractBee pollen and propolis are considered as health-promoting foods with many therapeutic (antibacterial, antifungal and antioxidant) activities. This study analyzed the phenolic profile and the antioxidant properties of Turkish bee pollen and propolis ethanolic extracts and assayed their antiproliferative effect on myeloma cells and in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity assays included agar well diffusion and microdilution methods. The phenolic profile and several aromatic compounds of the extracts were determined by high-performance liquid chromatography with diode-array detection (HPLC-DAD). The antiproliferative activity on myeloma cells was determined by MTT test. The propolis extract had higher total phenolic content (TPC), free-radical scavenging activity (DPPH) and half-maximal inhibitory concentration (IC50) than the pollen ethanolic extract. Benzoic and cinnamic acid were the most abundant aromatic substances in the pollen and propolis extracts, respectively. The IC50 values of pollen and propolis extracts on myeloma cells were 1.49% and 2.88%, respectively. The propolis extract was active against S. aureus and E. coli, but not P. aeruginosa. The pollen extract presented no detectable inhibition zone against the three bacterial strains. The minimum inhibitory concentration (MIC) of both extracts for S. aureus and E. coli was 0.63% (w/v). The minimum bactericidal concentration (MBC) of the propolis extract was 1.25% for S. aureus and E. coli. MIC could not be determined for the pollen extract in the tested bacteria. The pollen and propolis extracts did not exert antimicrobial activity against P. aeruginosa up to 2.5% concentration.

Cnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro. [ABSTRACT FROM AUTHOR]

It has been demonstrated that different organoboron compounds interact with some well-known molecular targets, including serine proteases, transcription factors, receptors, and other important molecules. Several approaches to finding the possible beneficial effects of boronic compounds include various in silico tools. This work aimed to find the most probable targets for five aromatic boronic acid derivatives. In silico servers, SuperPred, PASS-Targets, and Polypharmacology browser 2 (PPB2) suggested that the analyzed compounds have anticancer properties. Based on these results, the antiproliferative effect was evaluated using an in vitro model of triple-negative breast cancer (4T1 cells in culture). It was demonstrated that phenanthren-9-yl boronic acid and 6-hydroxynaphthalen-2-yl boronic acid have cytotoxic properties at sub-micromolar concentrations. In conclusion, using in silico approaches and in vitro analysis, we found two boronic acid derivatives with potential anticancer activity. [ABSTRACT FROM AUTHOR]

(1) Background: Hydrophobicity (or lipophilicity) is a limiting factor in the ability of molecules to pass through cell membranes and to perform their function. The ability to efficiently access cytosol is especially important when a synthetic compound has the potential to become a drug substance. D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2 (BIM-23052) is a linear analog of somatostatin with established in vitro GH-inhibitory activity in nanomolar (nm) concentrations and high affinity to different somatostatin receptors. (2) Methods: Series of analogs of BIM-23052 were synthesized where Phe residue(s) in the BIM-23052 molecule were replaced with Tyr using standard SPPS, Fmoc/t-Bu strategy. Analyses of target compounds were performed using HPLC/MS technique. Toxicity and antiproliferative activity were studied using in vitro NRU and MTT assays. The values of logP (partition coefficient in octanol/water) for BIM-23052 and its analogs were calculated. (3) Results: The obtained data show the best antiproliferative effect against studied cancer cells for compound D-Phe-Phe-Phe-D-Trp-Lys-Thr-Tyr7-Thr-NH2 (DD8), the most lipophilic compound according to the predicted logP values. (4) Conclusions: Multiple analyses of the obtained data reveal that compound D-Phe-Phe-Phe-D-Trp-Lys-Thr-Tyr7-Thr-NH2 (DD8) where one Phe is replaced by Tyr has the best combination of cytotoxicity, antiproliferative effect and hydrolytic stability. [ABSTRACT FROM AUTHOR]

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Introduction: The design and development of antitumor compounds based on an isatin core led to the synthesis of 1-substituted isatin-5-sulfonamides with potent antiproliferative activity [...]

Unlike MCF-7 cells, MDA-MB-231 cells are unresponsive to hormone therapy and often show resistance to chemotherapy and radiotherapy. Here, the antiproliferative effect of biocompatible montmorillonite (Mt) nanosheets on MDA-MB-231 and MCF-7 human breast cancer cells was evaluated by MTT assay, flow cytometry, and qRT-PCR. The results showed that the Mt IC50 for MDA-MB-231 and MCF-7 cells in a fetal bovine serum (FBS)-free medium was ~50 and ~200 µg/mL, and in 10% FBS medium ~400 and ~2000 µg/mL, respectively. Mt caused apoptosis in both cells by regulating related genes including Cas-3, P53, and P62 in MDA-MB-231 cells and Bcl-2, Cas-8, Cas-9, P53, and P62 in MCF-7 cells. Also, Mt arrested MCF-7 cells in the G0/G1 phase by altering Cyclin-D1 and P21 expression, and caused sub-G1 arrest and necrosis in both cells, possibly through damaging the mitochondria. However, fewer gene expression changes and more sub-G1 arrest and necrosis were observed in MDA-MB-231 cells, confirming the higher vulnerability of MDA-MB-231 cells to Mt. Furthermore, MDA-MB-231 cells appeared to be much more vulnerable to Mt compared to other cell types, including normal lung fibroblast (MRC-5), colon cancer (HT-29), and liver cancer (HepG2) cells. The higher vulnerability of MDA-MB-231 cells to Mt was inferred to be due to their higher proliferation rate. Notably, Mt cytotoxicity was highly dependent on both the Mt concentration and serum level, which favors Mt for the local treatment of MDA-MB-231 cells. Based on these results, Mt can be considered as an antiproliferative nanoagent against MDA-MB-231 cells and may be useful in the development of local nanoparticle-based therapies.

Blueberries are rich in flavonoids, anthocyanins, phenolic acids, and other bioactive substances. Anthocyanins are important functional components in blueberries. We collected 65 varieties of blueberries to investigate their nutritional and functional values. Among them, Gardenblue had the highest anthocyanin content, with 2.59 mg/g in fresh fruit. After ultrasound-assisted solvent extraction and macroporous resin absorption, the content was increased to 459.81 mg/g in the dried powder. Biological experiments showed that Gardenblue anthocyanins (L1) had antiproliferative effect on cervical cancer cells (Hela, 51.98 μg/mL), liver cancer cells (HepG2, 23.57 μg/mL), breast cancer cells (MCF-7, 113.39 μg/mL), and lung cancer cells (A549, 76.10 μg/mL), and no apparent toxic effects were indicated by methyl thiazolyl tetrazolium (MTT) assay, especially against HepG2 cells both in vitro and in vivo. After combining it with DDP (cisplatin) and DOX (doxorubicin), the antiproliferative effects were enhanced, especially when combined with DOX against HepG2 cells; the IC50 value was 0.02 μg/mL. This was further evidence that L1 could inhibit cell proliferation by inducing apoptosis. The detailed mechanism might be L1 interacting with DNA in an intercalation mode that changes or destroys DNA, causing apoptosis and inhibiting cell proliferation. The findings of this study suggest that L1 extract can be used as a functional agent against hepatoma carcinoma cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Gefitinib (GFB) was loaded into different designs of thermos- and pH-responsive polymer-based hydrogels, namely chitosan (CH) and Pluronic F127 (Pl F127) with the aid of a crosslinking β-glycerophosphate (β-GP). MATERIALS AND METHODS: GFB was loaded in CH and P1 F127 hydrogel. The preparation was characterized and tested for their stability and efficacy as antitumor injectable therapy devices. The antiproliferative effect of the selected CH/β-GP hydrogel formula was investigated against the hepatic cancerous cell, HepG2 using the MTT tetrazolium salt colorimetric assay. Furthermore, the pharmacokinetic was performed for GEF using a developed, reported and validated LC method. RESULTS: All hydrogel samples showed no changes in color, separation(s), and crystallization in both liquid and gel forms. The CH/β-GP system showed a lower viscosity (110.3 ± 5.2 Cp) compared to CH/β-GP/Pl F127 system (148.4 ± 4.4 Cp) in the sol phase. Also, the results confirmed a continued increase in rats' plasma during the first four days (Tmax) with a plasma peak level (Cmax) of 3.663 μg/mL followed by a decrease below the detection limit after 15 days. Moreover, the results indicated no significant difference (p < 0.05) between the predicted and observed GEF-concentration data and that the proposed CH-based hydrogel facilitated its sustained release as distinguished from the longer value of MRT of 9 days and an AUC0-t of 41.917 μg/L/day. CONCLUSIONS: The medicated CH/β-GP hydrogel formula had a higher targeting-controlled efficiency against a solid tumor than the free poor water soluble GFB. [ABSTRACT FROM AUTHOR]

2-Phenylethylammonium (PEA) salt derivatives have been prepared between 2-phenylethylamine with various aromatic carboxylic acids (nicotinic, benzoic, salicylic, and γ-resorcylic) and confirmed by spectroscopic analyses. Additionally, the possible biological activities of these salts have been examined and the antiproliferative and antimigrative effects of salts on breast and colon cancer cell lines have been determined. Furthermore, to obtain preliminary data for the effects of the indicated compounds on cancer angiogenesis, in vitro migration analysis has been performed by human vascular endothelial cells. The antibacterial effects of the compounds have also been investigated. Therefore, an important contribution has been made to studies conducted to better recognize the pharmacological effects of salts. [ABSTRACT FROM AUTHOR]

Plants are rich in bioactive phytochemicals that often display medicinal properties. These can play an important role in the production of health-promoting food additives and the replacement of artificial ones. In this sense, this study aimed to characterise the polyphenolic profile and bioactive properties of the decoctions, infusions and hydroethanolic extracts of three plants: lemon balm (Melissa officinalis L.), sage (Salvia officinalis L.) and spearmint (Mentha spicata L.). Total phenolic content ranged from 38.79 mg/g extract to 84.51 mg/g extract, depending on the extract. The main phenolic compound detected in all cases was rosmarinic acid. The results highlighted that some of these extracts may have the ability to prevent food spoilage (due to antibacterial and antifungal effects) and promote health benefits (due to anti-inflammatory and antioxidant capacities) while not displaying toxicity against healthy cells. Furthermore, although no anti-inflammatory capacity was observed from sage extracts, these stood out for often displaying the best outcomes in terms of other bioactivities. Overall, the results of our research provide insight into the potential of plant extracts as a source of active phytochemicals and as natural food additives. They also support the current trends in the food industry of replacing synthetic additives and developing foods with added beneficial health effects beyond basic nutrition. [ABSTRACT FROM AUTHOR]

Among the non-platinum antitumor agents, gold complexes have received increased attention owing to their strong antiproliferative effects, which generally occur through non-cisplatin-like mechanisms of action. Several studies have revealed that many cytotoxic gold compounds, such as N-heterocyclic carbene (NHC)-gold(I) complexes, are potent thioredoxin reductase (TrxR) inhibitors. Many other pathways have been supposed to be altered by gold coordination to protein targets. Within this frame, we have selected two gold(I) complexes based on aromatic ligands to be tested on cancer cells. Differently from bis [1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]gold(I) bromide (Au4BC), bis [1-methyl-3-acridineimidazolin-2-ylidene]gold(I) tetrafluoroborate (Au3BC) inhibited TrxR1 activity in vitro. Treatment of Huh7 hepatocellular carcinoma (HCC) cells, and MDA-MB-231 triple-negative breast cancer (TNBC) cells, with Au4BC inhibited cell viability, increased reactive oxygen species (ROS) levels, caused DNA damage, and induced autophagy and apoptosis. Notably, we found that, although Au3BC inhibited TrxR1 activity, no effect on the cell viabilities of HCC and BC cells was observed. At the molecular level, Au3BC induced a protective response mechanism in Huh7 and MDA-MB-231 cells, by inducing up-regulation of RAD51 and p62 protein expression, two proteins involved in DNA damage repair and autophagy, respectively. RAD51 gene knock-down in HCC cells increased cell sensitivity to Au3BC by significant reduction of cell viability, induction of DNA damage, and induction of apoptosis and autophagy. All together, these results suggest that the tested NHC-Gold complexes, Au3BC and Au4BC, showed different mechanisms of action, either dependent or independent of TrxR1 inhibition. As a result, Au3BC and Au4BC were found to be promising candidates as anticancer drugs for the treatment of HCC and BC. [ABSTRACT FROM AUTHOR]

Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC50 values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin. [ABSTRACT FROM AUTHOR]

The chemical compositions of four commercial essential oils were investigated using gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS) in this study. The prostate cancer cell lines PC3 and LNCaP were used to test the antiproliferative activities of the four essential oils using crystal violet staining. p-Cymene (14.2%), limonene (11.6%), and elemol (10.8%) were identified as the main compounds in Elemi-A. Limonene (36.4%), terpinolene (11.2%), and α-phellandrene (10.3%) were the major constituents in Elemi-B. α-Pinene (22.9%) and α-thujone (14.5%) were the main compounds of Frankincense-A. α-Thujone (35.4%) was the main compound in Frankincense-B. Three essential oil samples (Elemi-A, Elemi-B, and Frankincense-A) had minimum inhibitory concentration (MIC) values under 2 mg/mL against Bacillus subtilis and displayed noteworthy antibacterial activity. Additionally, Elemi-A had MIC values under 2 mg/mL against B. cereus and Pseudomonas aeruginosa. Moreover, Elemi-B had MIC values under 2 mg/mL against P. aeuroginosa. Elemi-B and Frankincense-B had dose-dependent and significant antiproliferative effects with IC50 values of 266.7 μg/mL and 230 μg/mL, respectively, against PC3 cells. The IC50 values of Elemi-A and Frankincense-A in the PC3 cells were 821.6 and 537.7 μg/mL, respectively. Only Elemi-B displayed a dose-dependent antiproliferative effect in the LNCaP cells with an IC50 value of 235.4 μg/mL. The present study determined the chemical composition of the essential oil of Elemi of French origin for the first time. Additionally, the antiproliferative activities of four essential oils against PC3 and LNCaP cells were first reported. Elemi-B, with the lowest IC50 values in the LNCaP and PC3 cells, had promising anticancer potential. [ABSTRACT FROM AUTHOR]

The production of fruit distillates generates solid residues which are potentially rich in bioactive compounds worthy of valorization and exploitation. We report herein the in vitro antioxidant and antiproliferative properties of an extract obtained from the waste of fermented strawberry distillate production. The main low molecular weight phenolic components of the extract were identified as ellagic acid and p-coumaric acid using spectroscopic and chromatographic analysis. The extract exhibited high antioxidant properties, particularly in the ferric reducing/antioxidant power (FRAP) assay, and a high total phenolic content (TPC). It was also able to induce an antiproliferative effect on different human cancer cell lines. A strong decrease in viability in human promyelocytic leukemia (HL-60) cells through a rapid and massive apoptosis were observed. Moreover, at an early time (<30 min), reactive oxygen species (ROS) production and inactivation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway were detected. Notably, the antiproliferative activity of the sample was comparable to that observed with an analogous extract prepared from unfermented, fresh strawberries. These results bring new opportunities for the valorization of fruit distillery by-products as low-cost resources for the design of bioactive formulations of comparable value to that from fresh food. [ABSTRACT FROM AUTHOR]

Garlic (Allium sativum L.) is a type of agricultural product that is widely used as a food spice, herb and traditional medicine. White garlic (WG) can be processed into several kinds of products, such as green garlic (GG), Laba garlic (LAG) and black garlic (BG), which have multiple health effects. In this study, GC-MS (gas chromatography-mass spectrometry), DPPH (1,1′-diphenyl-2-propionyl hydrazide) radical scavenging, hydroxyl radical scavenging and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) in vitro assays were used to compare the composition, antioxidant and antiproliferation effects of different processed garlic extracts. The relationship between the constituents and the bioactivities was analyzed using the principal components analysis (PCA) and heatmap analysis. BG showed the highest antioxidant activity (IC50 = 0.63 ± 0.02 mg/mL) in DPPH radical assays and the highest antioxidant activity (IC50 = 0.80 ± 0.01 mg/mL) by hydroxyl radical assay. Moreover, GC-MS results showed that 12 organosulfur compounds were detected in the extracts of four garlic products, and allyl methyl trisulfide showed a positive relation with the anticancer activity on SMMC-7721 cells (hepatocellular carcinoma cells). The results suggested that the processing of garlic had a significant influence on the constituents and antioxidant effects and that GG, LAG and BG might be better candidates for the related functional food products compared to WG. [ABSTRACT FROM AUTHOR]

Objective and Methods: The purpose of this article was to compare the extraction efficiency of bioactive compounds from Muntingia calabura peel using conventional methodology and ultrasound assistance, in addition, to verify the best extraction conditions, varying the drying temperature of the peels, time and solvents, and then to verify the cytotoxic and antiproliferative action of M. calabura extracts by Allium cepa. Results and Conclusions: It was verified through the analysis of total phenolic compounds, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) and iron reduction capacity that the best conditions were ultrasonic extraction, with a temperature of 50 °C, 50% aqueous ethanol solution and extraction time of 60 min. Regarding the quantification of total phenolic compounds (TPC), ABTS and ferric reducing antioxidant power (FRAP) in calabura peel, there was a variation of 571.33–1444.67 mg GAE (gallic acid equivalents) 100 g−1 dry peel for TPC, 19.36–115.74 mg Trolox 100 g−1 for ABTS and 306.73–1608.97 for FRAP. Regarding the cytotoxic effect on root growth of A. cepa, it was found that both conventional and ultrasound‐assisted extraction had an effect on onion root growth. In addition, together with the results of the analyzed cells and the literature, it can be verified that M. calabura peels also have an antiproliferative effect. This effect is due to the high concentration of phenolic compounds found in the analyzed extracts; such bioactive compounds are responsible for inhibiting cell division in meristematic cells. © 2022 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Several studies have suggested that increased consumption of phytochemicals is a comparatively easy and practical strategy to significantly decrease the incidence of cancer. In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice. B(a)P (50 mg/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20 mg/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P‐induced lung cancer‐bearing animals displayed cachexia‐like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma‐glutamyl transpeptidase, 5′‐nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P‐induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P‐induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P‐induced animals downregulated phosphatidylinositol 3‐kinase/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase‐3, and p53 with a parallel increase in antiapoptotic Bcl‐2. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P‐induced experimental lung tumorigenesis. [ABSTRACT FROM AUTHOR]

Proteins are the second most essential macromolecules after nucleic acids. This article aimed at the comparative analysis of extraction methods and nutritional benefits of milk and dairy products. Proteins form the body mass and perform several crucial tasks that include acting as a catalyst and carrying out different metabolic reactions in the body. Furthermore, protein acts as a transporter, transmits nerve impulses, provides mechanical support or immune protection, and controls growth. Several sources of proteins are present, but milk holds an important place due to its biological activities. The considerable health benefits of milk and its products are due to proteins. Yoghurt and cheese have significant importance among milk products. Proteins of milk and its products can be extracted by pH adjustment through homogenisation, centrifugation, and deproteinisation. There are several techniques for identifying and quantifying milk and product proteins. The Kjeldahl and spectrophotometric methods are the most widely used methods for quantifying proteins in milk and its products. Furthermore, these techniques include electrophoresis and chromatographic methods, including native gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), urea-PAGE, capillary electrophoresis, and isoelectric focusing. A few are chromatographic methods like reverse-phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography, and ion-exchange chromatography. Each technique has its advantages as well as disadvantages. The selection of the process depends upon the type of protein. The extracted proteins from milk and its products have many health or therapeutic effects that exhibit antimicrobial, antiproliferative, antioxidant, antihypertensive, anticancer, antiviral, and immunomodulatory effects. Yoghurt has prime importance among milk products because of its therapeutic effects and more protein.

Globularia alypum L. (GA) belonging to the Globulariaceae family is a Mediterranean plant which is widely used in traditional Tunisian medicine. The aim of this study was to investigate the phytochemical composition, antioxidant, anti-arthritic, antiproliferative, antibacterial and antibiofilm potential of aqueous GA leaf extracts (AGAL). Quantitative analyses of the different constituents of extracts were evaluated by high-performance liquid chromatography with photodiode-array detection (HPLC-DAD). Spectrophotometric methods and chemical tests were used for antioxidant and anti-arthritic activities. The antiproliferative study was evaluated using colorectal cancer SW620 cells, while the antibacterial assessment and analysis of the antibiofilm effects were determined by the microdilution method and the crystal violet assay, respectively. AGAL extracts presented several components, mainly Nepetin-7-Glucoside and trans-ferrulic acid. The results showed that they had an important antioxidant (IC50 = 0.34; 0.38 and 1.20 mg/mL) and anti-arthritic (IC50 = 2.94 mg/mL) properties, and these effects are displayed in a dose-dependent manner. In addition, this extract demonstrated significant antiproliferative (IC50 = 50 µg/mL), antibacterial (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties especially against S. aureus. The results achieved confirm the important role of this plant as a source of therapeutic activities.

The newly synthesized quinoline–benzimidazole hybrids containing two types of triazole-methyl-phenoxy linkers were characterized via NMR and elemental analysis. Additional derivatization was achieved by introducing bromine at the C-2 position of the phenoxy core. These novel hybrids were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts), leukemia and lymphoma cell lines: Hut78, THP-1 and HL-60, and carcinoma cell lines: HeLa and CaCo-2. The results obtained, presented as the concentration that achieves 50% inhibition of cell growth (IC50 value), show that the compounds tested affect tumor cell growth differently depending on the cell line and the dose applied (IC50 ranged from 0.2 to >100 µM). The quinoline–benzimidazole hybrids tested, including 7-chloro-4-(4-{[4-(5-methoxy-1H-1,3-benzo[d]imidazol-2-yl)phenoxy]methyl}-1H-1,2,3-triazol-1-yl)quinoline 9c, 2-(3-bromo-4-{[1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 10e, 2-{4-[(1-{2-[(7-chloroquinolin-4-yl)amino]ethyl}-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 14e and 2-{3-bromo-4-[(1-{2-[(7-chloroquinolin-4-yl)amino]ethyl}-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 15e, arrested the cell cycle of lymphoma (HuT78) cells. The calculated ADMET properties showed that the synthesized compounds violated at most two of Lipinski’s rules, making them potential drug candidates, but mainly for parenteral use due to low gastrointestinal absorption. The quinoline–benzimidazole hybrid 14e, which was shown to be a potent and selective inhibitor of lymphoma cell line growth, obtained the highest binding energy (−140.44 kcal/mol), by docking to the TAO2 kinase domain (PDB: 2GCD).

Berry volatiles are responsible for the berry aroma but there is limited information available on the health-promoting activities of berry volatiles. The objectives of this study were to evaluate the chemical composition of volatile extracts from black raspberries, blueberries, and blackberries and investigate their antiproliferative effect and apoptotic mechanisms on A549 lung cancer cells. The chemical composition of three berry volatile extracts (BVEs) was identified by using gas chromatography-mass spectrometry. Cells were treated with different dilutions of three BVEs for 48 h and determined for cell proliferation and apoptosis. Total volatiles in BVEs were 1.6–3.2 mg/L. Two-fold diluted BVEs significantly inhibited cell proliferation after 48 h, inducing apoptosis (p < 0.05). Blackberry volatile extract significantly reduced the inactive form of apoptotic proteins, including poly adenosine diphosphate-ribose polymerase (PARP), procaspase-9, and procaspase-3 compared to the control (p < 0.05). Blueberry volatile extract showed higher apoptotic cell death (p < 0.05) with a slightly higher cell population in G0/G1 phase than other berries. These results showed that volatile extracts from three berries have the antiproliferative effect on human lung adenocarcinoma cells partially via apoptosis, suggesting that volatiles from three berries may have potential anti-cancer activity through apoptosis in lung cancer. [ABSTRACT FROM AUTHOR]

A precursor‐directed approach to access N‐hydroxyalkyl phenylbenzoisoquinolindiones (PBIQs) has been developed. Incubation of plant material of Xiphidium caeruleum with hydroxylamines of various chain lengths (C2, C4, C6, C8, C10 and C12) resulted in 11 new 5‐hydroxy‐ and 5‐methoxy PBIQs with different N‐hydroxyalkyl side chain lengths. The antiproliferative effect and the cytotoxicity against HUVEC, K‐562, and HeLa cell lines of 26 previously reported PBIQs and the 11 newly synthesized N‐hydroxyalkyl PBIQs was determined for the first time. The results revealed that introducing long‐chain N‐aliphatic amine moieties improved the antiproliferative effect and cytotoxicity of PBIQs when compared to derivatives with N‐amino acids as side chains. [ABSTRACT FROM AUTHOR]

An efficient general method for the synthesis of a wide family of α-aminophosphonate analogs of aspartic acid bearing tetrasubstituted carbons is reported through an aza-Reformatsky reaction of α-iminophosphonates, generated from α-aminophosphonates, in an umpolung process. In addition, the α-aminophosphonate substrates showed in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines A549 (carcinomic human alveolar basal epithelial cell) and SKOV3 (human ovarian carcinoma). In view of the possibilities in the diversity of the substituents that offer the synthetic methodology, an extensive profile structure–activity is presented, measuring IC50 values up to 0.34 µM in the A549 and 9.8 µM in SKOV3 cell lines. [ABSTRACT FROM AUTHOR]

• Methanol extract from Sarcophyte sanguinea bulb extract exhibited better antimicrobial activity compared to dichloromethane extract. • The extract further exhibited a potent antioxidant activity and notably higher quantities of 5-aminoimidazole-4-carboxamide-1-ád-ribofuranosyl 5′-monophosphate, phthalic acid and di(oct‑3-yl) ester. • Dichloromethane extract exhibited potent antioxidant activity in four different assays. Antibiotic resistance necessitates the need for continued search for new antimicrobial compounds. In this study, we report the antibacterial activity, cytotoxic, and antioxidant activity of Sarcophyte sanguinea subsp. piriei (Hutch.) B. The extracts were evaluated for antibacterial activity using the agar well diffusion, micro-dilution, minimum bactericidal concentrations (MBC) and lactate dehydrogenase (LDH) release assay. Furthermore, the cytotoxic effects of extracts were determined using MTT assay against Human Embryonic Kidney (HEK293), Human Breast Endocrine Cells (SKBR-3), Human Colorectal Carcinoma Cells (Caco-2) and Human Hepatocellular Carcinoma (HepG2) cells. The extracts were also assessed for antioxidant activity against 2,2-diphenyl-1-picryl hydrazyl (DPPH), 2–2′-Azino-di-[3-ethylbenzthiazoline sulfonate (ABTS), nitric oxide radicals and Fe2+ chelating assays. The methanol extract (MeOH) was subjected to GC-TOF-MS analysis. MeOH extract exhibited highest zone of inhibition (ZI) of 15.67 mm against Staphylococcus aureus. The extract further exhibited 67.0% inhibition against Escherichia coli in a lactate dehydrogenase (LDH) membrane damage assay. In the cytotoxicity assay, MeOH and DCM extracts had LC 50 value of 237 µg/ml and 221 µg/ml against SKBR-3 cell line respectively. Gas-chromatography time-of-flight mass spectrometry (GC/TOF-MS) analysis of methanol extract indicated the presence of 5-aminoimidazole-4-carboxamide-1-ád-ribofuranosyl 5′-monophosphate (36.827%), 3-O-methyl-d-glucose (36.827%) and phthalic acid, di(oct‑3-yl) ester (8.161%). Even though the investigated plant is suggested to have anticancer activities by traditional healers, the extracts had little inhibition on selected cancerous cell lines. Given the good antibacterial and antioxidant activity of the extracts, the plant may act as an immune booster and prevent infections in immunosuppressed cancer patients. Detected compounds may be influence the observed biological activity of the plant. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the biological activities of chrysin (CRY), curcumin (CUR), and ellagic acid (EA) by comparing the anti-proliferative, anti-migration effects, and apoptotic gene expressions between the three human cancer cell lines: lung (A549), liver (HEP3B), and breast (MCF-7) compared to normal human fibroblast cell line (L929). Antiproliferative effects of certain phenolic compounds were determined by the MTS assay. Cells were treated with different concentrations of the compounds for two consecutive days. Their effect on cell migration was evaluated using the wound-healing assay. Apoptosis was evaluated by Bax, Bcl-2, Cas-3, Cas-8, Cas-9, Cas-10, CDK 2, CDK4, CDK6, CCNB1, and CCND2 gene expressions. The MTS assay showed that the compounds had antiproliferative effects on A549, HEP3B, and MCF-7 cell lines in a dose- and time-dependent manner. All three compounds also suppressed the migration of the tumor cell lines, significantly increased the levels of apoptotic gene expression, and induced apoptotic cell death. This study shows that chrysin, curcumin, and ellagic acid could be considered promising chemotherapeutic agents in the treatment of lung, liver, and breast cancers. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are promising nanomaterials exhibiting anti-cancer effects. Green AuNPs synthesis using plant extracts can be used to achieve stable and beneficial nanoparticles due to their content of bioactive compounds. This research aimed to synthesize and evaluate the antiproliferative and caspase-3 activity induction of green AuNPs synthesized with common mullein (V. thapsus) flowers (AuNPsME) and castor bean (R. communis) leaves (AuNPsCE) ethanolic extracts in human HT29 and SW480 colorectal cancer cells. Their effect was compared with chemically synthesized AuNPs (AuNPsCS). The extracts mainly contained p-coumaric acid (71.88–79.93 µg/g), ferulic acid (19.07–310.71 µg/g), and rutin (8.14–13.31 µg/g). The obtained nanoparticles presented typical FT-IR bands confirming the inclusion of polyphenols from V. thapsus and R. communis and spherical/quasi-spherical morphologies with diameters in the 20.06–37.14 nm range. The nanoparticles (20–200 µg/mL) showed antiproliferative effects in both cell lines, with AuNPsCE being the most potent (IC50 HT29: 110.10 and IC50SW480: 64.57 µg/mL). The AuNPsCS showed the lowest intracellular reactive oxygen species (ROS) generation in SW480 cells. All treatments induced caspase 3/7 activity to a similar or greater extent than 30 mM H2O2-treated cells. Results indicated the suitability of V. thapsus and R. communis extracts to synthesize AuNPs, displaying a stronger antiproliferative effect than AuNPsCS. [ABSTRACT FROM AUTHOR]

In this investigation, Fe3O4 magnetic nanoparticles (MNPs) were prepared via a chemical coprecipitation reaction, and the surface of Fe3O4 MNPs was coated with silica by a sol-gel process. The surface of Fe3O4@SiO2 MNPs was modified by an antioxidant agent, trans-ferulic acid, to achieve water-soluble MNPs for biological applications. Fourier transform infrared spectroscopy (FT-IR) showed that the MNPs were successfully coated with SiO2 and ferulic acid (FA) ligand. The morphology of γ-Fe2O3@SiO2-FA MNPs was found to be spherical in images of transmission electron microscopy (TEM) and showed a uniform size distribution with an average diameter of 21 nm. The in vitro cytotoxic activity of γ-Fe2O3@SiO2-FA MNPs and FA were investigated against the human cancer cells (MCF-7, PC-3, U-87 MG, A-2780, and A-549) by MTT colorimetric assay. The cytotoxic effect of MNPs on all cancer cell lines was several times of magnitude higher compared to free FA except for A-549 cell lines. Furthermore, in vitro DNA binding studies were investigated by UV–vis and circular dichroism spectroscopies. [ABSTRACT FROM AUTHOR]