Search

Due to chronic inflammation, elevated cyclooxygenase (COX-2) level leads to tumorigenesis, proliferation, invasion, angiogenesis and metastasis. Therefore, suppression of COX-2 enzyme is a fascinating approach in cancer treatment. In the present study, natural product eugenol was modified to develop new 1,2,4-triazole derivatives as antiCOX-2 and antiproliferative agents. The structures of newly prepared derivatives were established using sophisticated analytical techniques. The antiproliferative result showed compound 10 to be equipotent to doxorubicin towards MDA-MB 231 and PC-3 cancer cells with IC50 1.42 and 5.69 μM, respectively and potent COX-2 inhibitor with IC50 0.28 μM. Compound 10 was also non carcinogenic, non mutagenic with good drug likeness property as depicted by in silico physicochemical and pharmacokinetic studies. The docking results against COX-2 protein showed highest binding energy for compound 10 which was found to be in consistent with the cytoxicity and COX-2 results. In conclusion, compound 10 could harness COX-2 and cell proliferation and could be a promising candidate in cancer therapy. [ABSTRACT FROM AUTHOR]

Preparative high-performance liquid chromatography (HPLC) purification of the ethyl acetate extract derived from dried basidiomes of the European mushroom Hericium coralloides led to the identification of two previously undescribed isoindolinone derivatives named corallocins D and E (1-2). The structures of the compounds were elucidated based on HR-ESI-MS (high-resolution electron spray ionization mass spectrometry), interpretation of 1D and 2D NMR spectra, electronic circular dichroism (ECD) experiments, and comparisons with published and theoretical data. The metabolites were tested for their cytotoxic and antimicrobial effects in vitro where weak to moderate biological effects were observed against HeLa cells (KB 3.1), Mucor hiemalis and Bacillus subtilis. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance of microorganisms and the unwanted side effects of chemoradiation therapy in cancer are major issues in healthcare. In recent times, protein-based drugs have emerged as promising candidates due to their high specificity, less side effects, etc. In this context, the rhizome of Trillium govanianum was first explored for biologically active proteins/peptides. For this, three protein fractions namely Aqueous protein fraction (APF), Hexane-Methanol-treated aqueous protein fraction (HMAPF), and Methanol-treated aqueous protein fraction (MAPF) were prepared and evaluated for antimicrobial and antiproliferative activities. In antifungal activity, HMAPF showed the lowest MIC90 values of 1.56 µg/ml against Candida parapsilosis and Candida glabrata and 3.12 µg/ml against Candida albicans and Candida auris. The antifungal activity was further confirmed by a chitinase assay, a growth kinetics and a proteinase inhibitory assay. Surprisingly, none of the three protein fractions exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. Moreover, APF exhibited potent antiproliferative and antioxidant activities with IC50 values of 18 µg/ml and 227 µg /ml, respectively. For HMAPF, an IC50 value of 70 µg/ml against the MDA-MB-231 cell line was observed. The present results demonstrate that the protein fractions, particularly HMAPF and APF, might serve as potential sources of a dual antifungal and antiproliferative protein-based drug. [ABSTRACT FROM AUTHOR]

A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,β-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were − 6.6320 kcal/mol (with RMSD of 0.9477 Å) and − 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties. [ABSTRACT FROM AUTHOR]

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs. [ABSTRACT FROM AUTHOR]

(R)/(S)-the two enantiomers of 3-substituted-1-[2-(5)-3-substituted-4-benzyl-5-oxo-4-phenyl-2-thioxoimid-azolidin-1-yl]ethyl/propyl-5-benzyl-5-phenyl-2-thioxoimidazolidin-4-ones were formed during the diastereoselective reaction between N,N″-1,ω-alkanediylbis[N′-organylthiourea] derivatives and 2,3-diphenylcyclopropenone in refluxing ethanol. The structures of the isolated compounds were confirmed by NMR, IR, mass spectra and elemental analyses. Moreover, single-crystal X-ray structure analysis was also used to elucidate the structure of the isolated compounds. The mechanism describes the reaction was also discussed. The tested compounds showed EGFR inhibitory activity with IC50 values ranging from 90 to 178 nM in comparison to the erlotinib as a reference with IC50 value of 70 nM. Compound 4c (R = allyl, n = 3) was found as the most potent antiproliferative, had the highest inhibitory effect on EGFR with an IC50 value of 90 nM, compared to erlotinib's IC50 value of 70 nM. The second and third-most active compounds were 4e (R = phenyl, n = 3) and 4d (R = ethyl, n = 3) and with IC50 values of 107 nM and 128 nM. These findings imply that the compounds tested had a significant antiproliferative effect as well as the ability to act as an EGFR inhibitor. Docking studies showed that compound 4c showed high affinity to EGFR based on its docking score (S; kcal/mol) within five test compounds. [ABSTRACT FROM AUTHOR]

A new quinoline–thiosemicarbazone derivative, 5,7-dichloro-8-hydroxyquinoline-2-carboxaldehyde-4-phenyl-3-thiosemicarbazone (QPS) and seven complexes of QPS with d-transition metals (Mn, Fe, Co, Ni, Cu, Zn, Cd) were successfully synthesized. Spectrometry methods such as IR, ESI-MS, and 1H NMR were utilized to determine the structure of complexes that almost all complexes form the metal:ligand ratio of 1:1, except for FeQPS, which forms a 1:2 ratio. The center metals bond to QPS through O, Nquinoline and Nthiosemicarbazone. Four tested complexes (MnQPS, CoQPS, NiQPS, CuQPS) show medium inhibition to KB and Hep-G2 cancer cell lines. ZnQPS has the high activity against KB and Hep-G2 (IC50 = 13.51 and 10.28 μg/mL) and a high impact against the LU cancer cell line (IC50 = 2.0 μg/mL). CdQPS complexes showed excellent activity on both KB and Hep-G2 with IC50 very low, IC50 = 3.12 and 3.06 μg/mL, which is much lower than cisplatin. [ABSTRACT FROM AUTHOR]

Cancer is considered most detrimental due to high mortality worldwide. Among them, skin cancers play a major part by affecting one in three cancer patients globally. About 2–3 million cancer cases were reported to be non-melanoma and melanoma skin cancers, respectively. Although chemotherapeutic drugs act on cancer cells but results in long-lasting morbidities which affects one's quality of life and also works only in the initial stage of the cancer. Hence, an idea of traditional medicine to cure the disease efficiently with less side effects was pursued by the researchers. We have assessed the combination effect of p-coumaric acid and naringin in exerting anticancer activity using A431 (epidermoid carcinoma) cells. The MTT analysis of the combination on A431 cells showed the least IC50 concentration of 41 µg/ml which is effective than the standard drug imiquimod with IC50 concentration of 52 µg/ml. Further, flow cytometric analysis was carried out to identify the molecular mechanism behind the anticancer effects of the combination. The results revealed that the combination arrested the A431 cell cycle at S phase, induced apoptosis as indicated by more early and late apoptotic cells when compared with the control, and further altered reactive oxygen species (ROS) and mitochondrial membrane potential in A431 cells. Hence, the results suggest the potential anticancer effects of p-coumaric acid and naringin combination against the skin cancer (A431) cell line. The observed effects may be additive or synergistic effects in inducing ROS generation and apoptosis, and reducing the viability of A431 cells. [ABSTRACT FROM AUTHOR]

Conjugation of glycosyl isothiocyanates and steroidal amino alcohol derived from estrone, followed by an oxidative cyclodesulfuration reaction allowed the synthesis of a new class of bioactive molecules. This rapid and versatile protocol represents a useful approach toward the synthesis of a wide variety of novel 2-aminobenzoxazoles. The glycoconjugates (mono- and disaccharides) were successfully obtained in good to excellent yields. The acetyl-protected and deprotected compounds were screened for antiproliferative activity against six human cancer cell lines; a total of eight compounds showed mild to moderate activity. Remarkably, both derivatives bearing a mannose moiety exhibited GI50 values at the low μM range. [ABSTRACT FROM AUTHOR]

In the present work, a series of 1,2,4-triazole derivatives are designed as combretastatin A-4 analogs with the 4-nitrophenyl group and different aliphatic alkyl substituents, the designed compounds were synthesized and characterized by FT-IR, 1H NMR,13C NMR spectroscopy, and mass spectrometry. The synthesized compounds were tested as antiproliferative agents against human cancer laryngeal (Hep-2) cell line, the cytotoxicity of the synthesized compounds was evaluated by the treatment of a human normal kidney (Vero) cell line. The obtained results revealed that compound 5c, which has a n-propyl substituent, is the most active one and has lowest cytotoxicity against normal cells. This compound has the lowest IC50 value within the tested series; consequently, compound 5c could be considered a promising antiproliferative agent and a good candidate for further pharmacological studies. Molecular docking studies were implemented to determine the affinity of the synthesized compound toward the colchicine binding site. [ABSTRACT FROM AUTHOR]

A series of chalcones were synthesized and characterized by different spectroscopic techniques. The antioxidant properties of the compounds were evaluated through different free radical-scavenging assays. It was observed that some compounds exhibited strong scavenging activity against nitric oxide, DPPH, and hydroxyl radicals. The synthesized compounds exhibited less cytotoxicity against the normal CHO cell line. The MTT assay exhibited that the compounds with per cent viability of cells (70–90% at 21 µM) inhibited the selected human cancer (MCF-7 and HepG2) cell lines more effectively as compared to standard doxorubicin (90–95% at 18 µM concentrations). Further, the ADME properties were calculated to conclude a list of safe and effective compounds. The molecular docking revealed that some compounds were the most effective compounds in inhibiting CDK2 and the interaction studies show the hydrogen bond interaction was found with LYS33, LEU83, and ASP145. Overall, these compounds were obtained as lead compounds as potential anticancer, antioxidant, and antiproliferative agents. [ABSTRACT FROM AUTHOR]

Chickpea (Cicer arietinum L) is an important pulse crop and a good source of nutrients and dietary phytochemicals. The objective was to explore the influence of processing on flavonoids and saponins of nine pigmented (red, black, green, brown and cream seed coat) Desi chickpea seeds. Besides, the potential antiproliferative effects of flavonoids and saponins retained in the soaked/cooked seeds against human Caco-2, HT-29 and MCF7 cancer cell lines were assessed. The phytochemicals were identified by HPLC-IT-MS and quantified by HPLC-DAD-ELSD. In chickpea seeds, eleven compounds were identified belonging to myricetin glucosides, soyasaponin βg and biochanin-A glucosides. The total average content of saponins, isoflavones and flavonols in raw chickpeas were 453–2072 µg/g, 1–38 µg/g, and 7–66 µg/g, respectively. The thermal processing caused a significant reduction of flavonoids but only the control Kabuli chickpea lose saponins. The phytochemicals in Desi chickpeas showed better antiproliferative effects against Caco-2, HT29 and MCF7 cancer cells than the Kabuli counterpart. Thus, the Desi chickpea seeds seem to be good candidates for further studies for the development of functional ingredients. [ABSTRACT FROM AUTHOR]

Purpose: Phellinus fastuosus (Lév.) S. (Hymenochaetaceae, Hymenochaetales, Agaricomycetes, Basidiomycota) is a member of wood-rotting polyporoid fungi that contains numerous metabolites reported with many medicinal properties and has been used in traditional medicine for the treatment of various diseases. Inspired by the medicinal properties of this polypore the present study on the antioxidant and antiproliferative potential of methanolic extract of Phellinus fastuosus using various in vitro assays was proposed. Methods: The extraction of the basidiocarp of Ph. fastuosus was done sequentially in hot water (Pfaq), methanol (Pfme) and ethyl acetate (Pfea) to obtain the respective extracts. The antioxidant potential of different extracts was examined with 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, Ferric ion reducing antioxidant power and Phosphomolybdate assay. The cytotoxicity activity was determined by using MTT assay in human epidermoid carcinoma cells (A431), human cervical cancer (HeLa cells), human osteosarcoma (MG-63) and normal epidermoid cells (L929). For the assessment of changes in cell morphology, and apoptotic induction in A431 cell line was further investigated using phase-contrast microscopy, Hoechst 33342 staining and AO/EtBr dual staining. Flow cytometry was used for the estimation of production of reactive oxygen species (ROS) andmitochondrial membrane potential (MMP). Results: Among all, Pfme extract showed effective free radical scavenging potential in DPPH assay, as compared to the other extracts. Therefore the Pmfe extract was further evaluated for the antiproliferative activity in A431, HeLa and MG-63 cell lines. This extract was very effective in A431 with GI50 (growth inhibitory dose 50%) value of 81.39 compared to its effect in HeLa and MG-63 cells with GI50 values of 173.47 and 191.53 μg/ml respectively. The Pfme extract was further investigated to explore its role in apoptosis induction in A431 cell line. Phase-contrast and fluorescence microscopic studies exhibited all the characteristics indicative of apoptosis, viz., shape change, cell shrinkage, cell rounding-off and nuclear condensation. To understand the cause of effectiveness of Pfme extract, HPLC analysis was carried out which showed the presence of different polyphenols. Conclusions: A critical examination of results highlighted that the Pmfe extract induced apoptosis in A431 cells via ROS-mediated apoptotic pathway which may be ascribed to the presence of polyphenols in it. [ABSTRACT FROM AUTHOR]

Cancer is a broad collection of diseases that can begin in almost any organ or tissue of the body. Corn silk is the hair-like stigmata of female maize flowers which is generally discarded as waste from maize cultivation. The current study targets the anti-cancer potential of corn silk and its bioactive compounds namely, polyphenols, flavonoids, and sterols. The polyphenols and flavonoids like quercetin, rutin, apigenin and beta-sitosterol are a range of compounds from corn silk which were investigated for their anticancer effect. Corn silk showed apoptotic and antiproliferative effects in cancer cells through different signalling pathways, essentially the serine/threonine kinases (Akt)/lipid kinases (PI3Ks) pathway. The study revealed that corn silk compounds target immune cell responses, induce cell cytotoxicity, and upregulate the expression of proapoptotic genes p53, p21, caspase 9, and caspase 3 in certain cancer cell lines including HeLa cervical cancer cells, MCF-7 breast cancer cells, PANC-02 pancreatic cancer cells and Caco-2 colon cancer cells. Flavonoids derived from corn silk enhance T cell mediated immune response and decrease inflammatory factors. Corn silk bioactive compounds were found to reduce the side effects of cancer therapy. Antioxidants of corn silk, quercetin and rutin help in reducing the nephrotoxicity of chemotherapeutic drugs. The study also suggests that corn silk has anti-cancerous potential as it targets tumour suppression and inhibits metastasis A dose of 500 mg/kg body weight of corn silk has been found safe for human consumption. Corn silk extract can be used as a preventive or therapeutic step to cure cancer. The anti-cancer property, mechanism and role of corn silk in controlling cancer-related side effects have been critically reviewed providing new scope for the use of corn silk in cancer therapy. [ABSTRACT FROM AUTHOR]

Various Chiliadenus species are extensively dispersed in Palestine and were used in ancient medicine to cure a variety of illnesses. In this regard, the goal of the present study was to characterize Chiliadenus sericeus subsp. virescens (CVS) lipophilic and hydrophilic extracts phytoconstituents and estimate their antimicrobial, antioxidant, antidiabetic, and antiproliferative capabilities. The chemical assessments were determined using standard analytical techniques. The CVS extracts antimicrobial characteristics were estimated using the microdilution method against seven microbial species. Diphenylpicrylhydrazine (DPPH) free radical and α-amylase inhibitory assays were used to assess the extract's antioxidant and antidiabetic capabilities. Furthermore, the MTT colorimetric approach was used to evaluate cell viability and proliferation in different cell lines. The hydrophilic extract suppressed the growth of Methicillin-resistant Staphylococcus aureus (MRSA) strains, making it even more effective than the antibiotic ciprofloxacin. In the case of Staphylococcus aureus, CSV hydrophilic extract at a dose of 2 mg/ml has more potent activity than ampicillin at the same dose. In addition, it has the same inhibitory effect as Fluconazole against Candida albicans. Moreover, compared to Trolox, the hydrophilic extract demonstrated significant antioxidant activity with an IC50 of 15.13 ± 0.72 μg/ml. In addition, the lipophilic extract demonstrated remarkable α-amylase enzyme inhibitory action compared to acarbose. Finally, the lipophilic extract shows cytotoxic effects on all cancer cells examined. Our findings suggest that CSV lipophilic and hydrophilic extracts might be a potential synthetic drugs alternative treatment for oxidative stress-induced illnesses, diabetes, microbial infections, and cancer. [ABSTRACT FROM AUTHOR]

In this study, it was aimed to evaluate the cytotoxic and apoptotic activities of ethanolic extracts prepared from the roots of 5 Ferulago species [F. humilis Boiss., F. macrosciadia Boiss. & Balansa, F. sandrasica Peşmen & Quézel, F. silaifolia (Boiss.) Boiss., F. trojana Akalın & Pimenov] on various human cancer cell lines. The cytotoxicity analyses against human lung (A549), breast (MCF-7), prostate (PC3) and colon (SW480) cancer cell lines were determined by MTT test; while the apoptotic effect was evaluated by Annexin V binding assay. All studied extracts showed concentration-dependent cytotoxic activity with an IC50 value ranging from 0.416 to 5.336 mg/mL. The studied Ferulago species significantly induced apoptosis of cancer cells, while F. macrosciadia had the highest apoptotic activity on MCF-7 cells with 21.79 ± 1.63% apoptotic cell population (p < 0.0001). In addition, felamedin and prantschimgin content of the extracts, which are common coumarins in Ferulago species, were evaluated by HPLC. According to HPLC analysis, the highest amount of felamedin content was found in F. trojana, while the highest content of prantschimgin was found in F. sandrasica among the studied Ferulago species. This preliminary research has revealed that the studied Ferulago species have promising effects on various cancer cell lines. Further studies are planned to determine the compounds responsible for the effect and underlying mechanism. [ABSTRACT FROM AUTHOR]

Taking coconut peel as raw material, the extraction process of coconut peel polysaccharide (CPP) was optimized by boiling water extraction. The coconut peel polysaccharide was characterized by UV, IR, SEM, 1D NMR and 2D NMR spectra. At the same time, the molecular weight and monosaccharide component were analyzed by gel chromatography and ion chromatography, respectively. Antioxidant activity of coconut peel polysaccharide and its derivatives in vitro was evaluated by scavenging ABTS and DPPH radicals and O2−·, and the anti HepG2 proliferation activity in vitro was also carried out. The results showed that the molecular weight of coconut peel polysaccharide was 1.20 × 105 Da, which was mainly composed of arabinose (Ara), galactose (Gal), glucose (Glu), xylose (Xyl) and galacturonic acid (Gal-A). The main chain structure of polysaccharides detected by 1D and 2D NMR spectrum was → 4)-α-D-Glcp (1 →. In vitro antioxidant test showed that coconut peel polysaccharide and its derivatives had a certain scavenging effect on ABTS and DPPH free radical and O2−·. With the increase of polysaccharide concentration, the scavenging ability was gradually increased. In addition, coconut peel polysaccharide and its derivatives showed significant antiproliferative activity against HepG2 cells in vitro. [ABSTRACT FROM AUTHOR]

In this study, the antioxidant activity of Alcea kurdica (Schltdl.) Alef. was investigated to reduce the effects of oxidant compounds. In addition, DNA protecting activity, antiproliferative activity, antibacterial, antifungal activities, phenolic contents, and chemical compositions of plant extracts were determined. Plant samples were collected from Zakho (Iraq). In addition, methanol (MeOH) and dichloromethane (DCM) extracts of the root parts of the plant were obtained. As a result of our studies, it was determined that A. kurdica has important biological activities. In addition, it was determined that Gallic acid, Syringic acid, Chlorogenic acid, and Quercetin was within the plant. In addition, 12 compounds were determined as a result of GC-MS analysis. As a result, it has been determined that it can be used to reduce the effect of oxidative stress from plant samples. In addition, it is also thought to be an important pharmacological natural agent. [ABSTRACT FROM AUTHOR]

Castor oil was autoxidized for three months to obtain macroperoxide castor oil (PCO). Since this polymeric oil has peroxide groups and hydroxyl groups, free-radical polymerization (FRP), ring-opening polymerization, and one-pot polymerization both free-radical polymerization (FRP) and ring-opening polymerization in one step methods were used to synthesis of various types of the graft copolymers. PCO-g-Polystyrene, PCO-g-Poly(methyl acrylate), and PCO-g-Poly(tert-buytl acrylate) were synthesized using the free-radical polymerization method. PCO-g-Poly(ε-caprolactone) graft copolymer was obtained via ring-opening polymerization, and PCO-g-Polystyrene-g-Poly(ε-caprolactone) graft copolymer was obtained using one-pot polymerization method. All graft copolymers obtained were characterized by proton nuclear magnetic resonance (1H NMR), Fourier-transform infrared, differential scanning calorimetry, thermal gravimetric analysis, and elemental analysis. After the synthesis of castor oil-based copolymers, we determined the antimicrobial effects of them as well as the antiproliferative effects on breast cancer cell lines. Antimicrobial activity was carried out using the disc diffusion method and the dilution method. As a result of antimicrobial activity, the compounds showed moderate antimicrobial effects on microorganisms compared to standard antibiotics. In particular, the compounds have shown more antibacterial activity than antifungal activity. We also observed a prominent antiproliferative effect of synthesized compounds depending on increasing doses (1–25 µg/mL) and times (24–48 h) in MDA-MB-231 breast cancer cells. [ABSTRACT FROM AUTHOR]

The present study aimed to determine antiproliferative, antimicrobial, antioxidant activities and also phytochemical composition of different nine Adonis L. species from Turkey. Leaves extracts of the plant samples were used to evaluate antimicrobial activity against 7 bacteria and 2 yeast strains using MICs and disc-diffusion methods. The antioxidant activity of plant samples was determined by using DPPH radical scavenging activity method. MTT assay was used for evaluation antiproliferative activities of the extracts against HL-60, HCA-7 and HUVEC human cells. Chemical composition of plant extracts were determined by Gas Chromatography/Mass Spectrometry. The antimicrobial analyses results showed Gram-negative bacteria more sensitive than Gram-positive against the extracts, and the values were varied from 3.1 to 13.4 μg/mL. The leaf extract of different Adonis species exhibited remarkable antiproliferative activities towards tested human cancer cells in a dose and time dependently, and they were found to possess more antiproliferative activity against HL-60 cells than that of the HCA-7 cells. As for the chemical composition of Adonis species, they were found to contain many components with antimicrobial and beneficial effects, such as ethyl palmitate, ethyl linoleate. Overall, it was concluded that leaves extracts of Adonis species could have a great potential for use in medicinal drug sources. [ABSTRACT FROM AUTHOR]

Purpose: Anabasis articulata (Forssk.) Moq. (Chenopodiaceae), also called Eshnan, Ajremor Berry bearing glasswort, is widely distributed in Syrian, Algerian, Jordan, Lebanon, Saudi Arabia, Egyptian and Iraqi desert, Spain (Alicante, Almería, Granada and Murcia provinces), Mauritania, Western Sahara and Morocco. Anabasis articulata is broadly used in folk medicine to treat diabetes, fever, eczema and kidney infections. The objective of this work was to examine the potential bioactivity of the plant, in vitro and in vivo experiment. Methods: The sterol-rich extract was identified by GC/MS analysis. The antioxidant potential, anti-tyrosinase and antiproliferative activities, was evaluated by in vitro assays and anti-inflammatory function was determined by in vivo assay. Results: The results revealed that the chromatographic analysis showed the presence of four sterols in the plant samples. A preliminary evaluation of the antiproliferative effect of A. articulata against two human tumor cell lines, MCF7 and MDA-MB 231, was evaluated by MTT assay. The plant extract was also subjected to four different in vitro antioxidant assays (i.e. total antioxidant capacity, reducing power, DPPH and β-carotene-linoleic acid bleaching). The sterol-rich extract also showed a high anti-tyrosinase activity, and an acetylcholinesterase inhibitory effect, and in vivo toxicological and anti-inflammatory function of A. articulata sterols was tested on rats with carrageenan-induced inflammatory paw edema. Conclusions: All this evidence suggests the possible application of the aerial part of A. articulata as food additive, in pharmaceutical and cosmetic industries. [ABSTRACT FROM AUTHOR]

Crude methanol extract (ME) of broccoli (Brassica oleracea L.) sprout was fractioned by hexane, chloroform, ethyl acetate, butanol, and water. The contents of total polyphenols (19.89 mg GAE/g) and flavonoids (10.06 mg RE/g) were significantly higher in the butanol fraction (BF) than in the other fractions. The BF showed the highest DPPH (EC50 = 0.524 mg/mL) and ABTS (EC50 = 0.180 mg/mL) radical scavenging activities. High-performance liquid chromatography (HPLC) of crude ME showed that the most abundant phenolic compounds were rutin, quercetin, chlorogenic acid, catechin, and p-coumaric acid. The contents of quercetin, chlorogenic acid and p-coumaric acid were higher in the ethyl acetate fraction (EF) and BF than in the other fractions. Antioxidant activity and phenolic compound contents were correlated, suggesting that phenolics were responsible for the antioxidant activity. The hexane fraction (HF) and chloroform fraction (CF) decreased the viability of breast cancer stem cells (BCSCs), and the CF had the highest antiproliferative activity (IC50 = 69.47 mg/mL). The CF also suppressed the stemness characteristics of BCSCs and induced apoptotic cell death. The most abundant characteristic peak in CF was identified as oleic acid (area = 35.05%) by gas chromatography-mass spectrometry (GC–MS). Therefore, the broccoli sprout BF contained high levels of phenolic compounds that contributed to its antioxidant activity, and CF had a marked anti-proliferative effect on BCSCs. [ABSTRACT FROM AUTHOR]

Background: Sea cucumber is a natural resource rich in many important pharmacological compounds. this study aimed to investigate the effect of H. leucospilota extract on the induction of cell death and and Proapoptotic Activities. Methods and Results: H. leucospilota was collected, the methanolic extract was prepared and in vitro cytotoxicity of H. leucospilota extract in the range of 12.5, 25, 50, 100, and 200 μg/mL concentrations for 48 hours on SK-BR-3 and MCR5 cells was determined. Analysis of apoptosis and cell cycle stages were performed using flow cytometry. the expressions of several apoptotic-related proteins in SK-BR-3 cells were evaluated using Western blot analysis. ROS formation and caspase activity were determined. GC-MS (involving a multistep temperature gradient and trimethylsilyl derivatives) and phytochemical analysis were used for identification of bioactive compounds. Methanolic extract inhibited the proliferation of the SK-BR-3 cell line in a dose- and time-dependent manner. As it was observed, exposure of the H. leucospilota extract triggered the apoptosis of the SK-BR-3 cells, induced DNA fragmentation, and arrested the cells in G2/M phase. treatment of the methanolic extract induced the downregulation of antiapoptotic Bcl-2 protein as well as the upregulation of Bax, caspase-3, caspase-7 proteins in SK-BR-3 cells. Methanolic extract-elicited apoptosis was accompanied with the elevated level of ROS. The GC-MS and phytochemical analysis revealed 30 compounds and the extract contained alkaloids, flavonoids, steroids, terpenoids, phenols, and saponins. Conclusions: The antiproliferative and proapoptotic activities of the tested extract suggested the pharmacologic potential of H. leucospilota. Correspondingly, further characterizations of the identified compounds are in progress. [ABSTRACT FROM AUTHOR]

In this research, a series of new phthalimide derivatives with disulfide bonds were designed and synthesized, and their in vitro antiproliferative activities against normal cell lines L929, human cancer cells Hela, MCF-7, and A549 were assessed via the CCK-8 assay. At the same time, in vitro antimicrobial activities of all compounds were evaluated against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. The preliminary bioassay results showed that a series of derivatives of phthalimide 6a–e, 7a–e, 8a–e, and 9a–e exhibited different degrees of antiproliferative activity, and some compounds revealed higher antiproliferative effects than the positive control 5-fluorouracil. Compound 9b (IC50 = 2.86 μM) exhibited the best proliferation inhibitory activities against A549 cells. It is shown that compounds 6b (IC50 = 2.94 μM) and 6c (IC50 = 3.20 μM) exhibited excellent biological activities against Hela cells. Compound 9b (IC50 = 3.21 μM) displayed the highest antitumor activities against MCF-7 cells. In addition, most of the target compounds had relatively low cytotoxicities against the normal cell line L929. The biological results indicated that all the tested compounds possessed antimicrobial activity with certain degrees against E. coli and S. aureus. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the most important reasons for mortality worldwide. Several synthetic products have shown valuable efficiency as an anticancer medicines. Chromene derivatives have long been used as the promising compounds which are potent in inhibition of the growth of tumors. Methods and results: In this study, we investigate an anticancer activity of barbituric/thiobarbituric acid-based chromene derivates. For this purpose, viability, antioxidant and apoptotic assays were conducted using three different cancer cell lines (A2780, MCF7, and A549). In most cases, the antiproliferative activity of barbituric acid-based derivatives was higher than that of thiobarbituric acid-based compounds. Among 14 compounds, compound 4g was the most potent one, which showed the highest effect on cells by increasing the accumulation of ROS (up to 540% increase), increasing the level of caspase-3 and caspase-9 (~ 35% increase), and decreasing the mitochondrial membrane potential (2.5 folds reduction). To characterize the type of cell death involved into our experiment Annexin V/PI double staining of compound 4g was performed. The results showed that the number of late apoptotic and/or necrotic cells (Ann V + /PI +) increased fourfold upon treatment with IC50 concentration of 4g. Conclusions: Overall, the anti-proliferative activity of barbituric acid-based derivatives was higher than that of thiobarbituric acid compounds, and compound 4g can be introduced as a potential candidate to prevent various cancers. [ABSTRACT FROM AUTHOR]

Alstonia scholaris, Cardiospermum halicacabum, Hydrocotyle sibthorpioides, and Hypericum japonicum are important folk medicinal plants used by tribal communities of Bodoland region of Assam to treat helminth infections. Because of their ethnomedicinal values, the present study was designed to investigate the antioxidant, antiproliferative, and anthelmintic activities of the plants. The antioxidant activity was measured by total antioxidant capacity, total phenolics (TPC), total flavonoid (TFC), FRAP, DPPH, ABTS, and TBARS assay. Antiproliferative and apoptosis-inducing activities of plants were conducted in Dalton's lymphoma (DL) cells. Cells were treated for 24 h with different doses (25–200 mg/mL) of plant extracts. Anthelmintic study was conducted by treating the Paramphistomum sp. at different doses of plant extracts. Phytochemical and antioxidant studies showed rich TPC, TFC, and free radical scavenging activity in H. japonicum and H. sibthorpioides. Both the antiproliferative and anthelmintic bioassays showed a dose-dependent efficacy in all plants. H. japonicum showed the strongest anthelmintic activity (LC50 0.21 mg/mL) followed by H. sibthorpioides (5.36 mg/mL), C. halicacabum (13.40 mg/mL), and A. scholaris (18.40 mg/mL). Evidently, H. sibthorpioides showed the strongest antiproliferative and apoptosis-inducing activities among all the plants. The study observed a positive correlation between the antioxidant properties and antiproliferative and anthelmintic activities of the plants. We, therefore, conclude that the phytocompounds present in the crude extracts along with antioxidant molecules may have combined effects contributing to the antiproliferative and anthelmintic activities of the plants. [ABSTRACT FROM AUTHOR]

Curcumin and cinnamaldehyde are natural products whose antineoplastic activity has been well explored in biological evaluations. However, their poor chemical stability under physiological conditions has been an obstacle to their use as therapeutic agents. Herein, we designed and synthesized two series of curcumin-cinnamaldehyde hybrids by removing reactive functionalities, including β-diketone and aldoxyl moieties. All compounds were evaluated by the MTT assay to determine their antiproliferative activity against women's cancer cells. Compound 5a (3′-hydroxychalcone) demonstrated potent antiproliferative activity against all cancer cell lines tested, with IC50 values ranging from 2.7 to 36.5 µM. Compound 5a was more active and selective than curcumin and cinnamaldehyde (parent compounds) against the CaSki, SiHa, C33, and A431 cell lines, displaying a higher selectivity index (SI = 8.5) than curcumin (SI = 0.8) toward the non-tumorigenic HaCaT cell line. Clonogenic experiments indicated that compound 5a inhibited A431 colony formation in a concentration-dependent manner. In addition, 5a was more stable than its parent compounds in pH 7.4 at 37 °C. In silico investigations suggested that 5a has good drug-likeness properties. In conclusion, our results indicate the use of curcumin and cinnamaldehyde as parent compounds for the design of hybrids with attractive antiproliferative activity and chemical stability. [ABSTRACT FROM AUTHOR]

Background: C. vespertiliomis extracts were evaluated for antiproliferative and apoptosis effect on breast cancer (MCF7) cells. Methods and results: The leaves extracts were analysed for its antiproliferative effect on breast cancer (MCF7) cells and normal epithelial breast (MCF 10A) cells using Sulforhodamine B (SRB) assay. The selective extract was evaluated for its ability to induce apoptosis using Annexin V-FITC apoptosis staining and the expression of molecular genes using qualitative reverse transcription-polymerase chain reaction (RT-PCR) against MCF7 cells. Gas chromatography–mass spectrometry (GC–MS) was used to identify the compounds from the selective extract. The findings showed that dichloromethane fraction (CV-Dcm) extract had high antiproliferative effect against MCF7 cells (IC50 = 24 µg/mL, selective index (SI) = 8.17). The percentages of apoptosis cells in CV-Dcm-treated MCF7 cells was 58.8%. The CV-Dcm extract induced downregulation of PCNA level. The apoptotic genes were also triggered in both extrinsic and intrinsic signaling pathways, affecting a 1.5-fold increase in BAX, 1.4-fold increase in cytochrome c, 1.3-fold increase in caspase-8, 1.7-fold increase in caspase-3 and 0.5-fold-decrease in BCL-2. Treated MCF7 cells also activated P53-dependent apoptotic death pathway. Conclusions: The present work strongly suggests that high efficacy of CV-Dcm extract was attributed to its antiproliferative and apoptosis-inducing activation in MCF7 cells, most likely due to its favourable compounds. [ABSTRACT FROM AUTHOR]

A series of substituted N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)thiosemicarbazones 5a–5j of substituted 3-acetylcoumarins were synthesized with yields of 45–68%. All synthesized thiosemicarbazones were evaluated for cytotoxic activity against several cancer cell lines, such as human breast adenocarcinoma cells MCF7, human liver cancer cells HepG2, human cervical cancer cells HeLa, human melanoma cancer cells SK-Mel-2, and human lung cancer cells LU-1 by using the standard MTT assay. The IC50 values for these cancer cell lines were 1.28–11.81 μM (for MCF-7), 1.53–22.12 μM (for HepG2), 1.43–48.16 μM (for HeLa), 1.82–14.62 μM (for SK-Mel-2), and 1.74–14.62 μM (for LU-1). Most of the compounds were noncytotoxic against human WI-38 normal cell line (IC50 > 16.9 μM). The antiproliferative mechanisms were studied via EGFR inhibition and molecular docking. Docking studies revealed that there are strong interactions between a typical compound with the receptor of the EGFR tyrosine kinase domain with Erlotinib. [ABSTRACT FROM AUTHOR]

Two series of 3-mercapto-1,2,4-triazole derivatives containing alkoxy substituents different in size and position were synthesized and their structures were characterized by FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The synthesized compounds were assessed for their antiproliferative activity against colon cancer cell line (SW480). The results indicated that the size and position of the alkoxy group significantly influenced the antiproliferative activity. The highest cancer cell growth inhibition values were observed for the compounds containing 3,4,5-trimethoxyphenyl groups in their structures (57.74, 54.14 and 60.70% at 50 μM for compounds 5a, 12b and 14, respectively). The synthesized compounds were also subjected to DPPH protocol for evaluating the antioxidant activity. The results showed that all compounds had moderate to high levels of antioxidant capacity as compared to ascorbic acid as standard, the highest free radical scavenging capacity of 75% was observed for compound 4a at 50 μM. [ABSTRACT FROM AUTHOR]

Onosma bracteata Wall. (Boraginaceae), commonly known as "gaozaban" is a highly valuable medicinal herb, useful in the treatment of body swellings, abdominal pain, eye-related problems, fever, and urinary calculi. The present study was performed to investigate the antioxidant properties of extract/fractions, viz. ethanol (Obeth) extract, hexane (Obhex) fraction, chloroform (Obcl) fraction, ethyl acetate (Obea) fraction, butanol (Obbu) fraction, and aqueous (Obaq) fraction isolated from O. bracteata. Obea fraction showed stronger free radical quenching ability in various antioxidant assays, as compared to the other fractions. Obea fraction with effective free radical-scavenging properties was further evaluated for the antiproliferative activity against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay. Obea fraction showed strong cytotoxicity with GI50 value of 88.56, 101.61, and 112.7 μg/ml towards MG-63, IMR-32, and A549 cells respectively. Mechanistic studies revealed that Obea fraction in osteosarcoma MG-63 cells increased reactive oxygen species (ROS) level and reduced mitochondrial membrane potential. In the presence of Obea, the cells were found to be arrested in the G0/G1 phase in a dose-dependent manner which is also confirmed by the enhancement in the early apoptotic cell population in flow cytometer analysis. Western blotting demonstrated the decrease in expression of p-NFκB, COX-2, p-Akt, and Bcl-xL, whereas upregulation was observed in the expression of GSK-3β, p53, caspase-3, and caspase-9 proteins. RT-qPCR studies revealed downregulation of Bcl-2, cyclin E, CDK2, and mortalin gene expression and upregulation in the expression of p53 genes. The antioxidant and cytotoxic potential of Obea was attributed to the presence of catechin, kaempferol, onosmin A, and epicatechin, as revealed by HPLC analysis. This is the first report regarding the antiproliferative potential of O. bracteata against osteosarcoma. [ABSTRACT FROM AUTHOR]

The pyrimidine scaffold is a versatile lead heterocycle in pharmaceutical development. It has diverse chemical reactivity, accessibility and a wide range of biological activities. In the past few years, the pyrimidine derivatives have been developed drastically as potent anticancer agents. This review highlights the current status of pyrimidine molecules in cancer therapy. The in vivo models have been enumerated for the specific types of cancer. The structure – activity relationship (SAR) of fused and substituted pyrimidine derivatives for anticancer activity is discussed. Electron withdrawing groups on aryl moiety attached to both substituted and fused pyrimidine influenced positively, and enhanced potency of novel small molecules as anticancer agents. Electron donating groups reduced the antiproliferative activity. Thus, scientists and researchers of medicinal chemistry discipline could design small molecules with a pyrimidine scaffold possessing more promising anticancer potential. [ABSTRACT FROM AUTHOR]

The present study investigated the antimutagenic, antioxidant, and antiproliferative properties of extracts of Cassia fistula prepared by sequentially fractionation of 80% methanolic (CaLM extract) extract of C. fistula leaves, namely CaLH (hexane), CaLC (chloroform), CaLE (ethyl acetate), CaLB (n-butanol), and CaLA (aqueous) fractions. The antimutagenicity of the fractions was tested against mutagens viz. S9-independent, namely 4-nitro-o-phenylenediamine (TA98) and sodium azide (TA100) and S9-dependent, 2-AF (2-aminofluorene). Among the tested fractions, CaLE fraction showed a potent efficacy with an inhibition percentage of 85.57% (TA98) and 89.93% (TA100) against the mutagenicity induced by 2-aminofluorene. The CaLE fraction could significantly scavenge free radicals in various assays, namely DPPH, lipid peroxidation inhibition, and superoxide anion radical scavenging assays with an IC50 of 12.80, 144, and 257.3 μg/ml respectively. The antiproliferative potential of the effective CaLE fraction was assessed using MTT assay against HeLa and MCF-7 cancer cells with GI50 value of 243.4 and 324.6 μg/ml respectively. The fraction exhibited remarkable apoptosis-inducing effects through the externalization of phosphatidylserine in HeLa cells as analyzed by annexin V-FITC/PI double staining assay. The HPLC analysis of CaLE revealed the presence of catechin, epiafzelechin, and chlorogenic acid which are responsible for its antimutagenic and antiproliferative efficacy. [ABSTRACT FROM AUTHOR]

Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola, and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention. This review summarizes the progress of recent research on the antiproliferative activities of salidroside and its effects on breast, ovarian, cervical, colorectal, lung, liver, gastric, bladder, renal, and skin cancer as well as gliomas and fibrosarcomas. Thus, it provides a reference for the further development and utilization of salidroside. [ABSTRACT FROM AUTHOR]

Based on the recent studies depicting the potential of heterometallic gold complexes as potent antiproliferative agents, herein we first reported the preliminary mechanistic data on the in-vitro antiproliferative activity of tricyclohexylphosphanegold(I) n-mercaptobenzoate, Cy3PAu(n-MBA) where n = 2 (1), 3 (2) and 4 (3), and MBA = mercaptobenzoic acid, treated using MCF-7 breast cancer and A2780 ovarian cancer cells, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to assess the cytotoxicity of both cancer cells treated with 1–3, respectively. The IC50 of 1–3 were applied to the subsequent assays including cell invasion and thioredoxin reductase (TrxR) as well as ubiquitin activities specifically on Lys48 and Lys63-linked polyubiquitin chains via flowcytometric analysis. The mechanistic effect of 1–3 towards both cells were evaluated on human p53 signaling gene expressions via RT2 profiler Polymerase Chain Reductase (PCR) array. 1–3 were found to be highly cytotoxic towards both MCF-7 and A2780 cancer cell lines with the compounds were more sensitive towards the latter cells. 1–3 also suppressed TrxR and cell invasion activities by modulating p53 related genes related with proliferation, invasion and TrxR activities i.e. CCNB1, TP53, CDK4 etc. 1–3 also regulated Lys48 and Lys63-linked polyubiquitination by reactivation of p53, suggesting the ability of this gene in regulating inhibition of cytoskeletal reorganization via epithelial–mesenchymal transition (EMT), required for tumor progression. Taken together, the overall findings denoted that 1–3 exerted potent antiproliferative activity in MCF-7 and A2780 cells via activation of the p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Cashew apple extract (CAE) is a product with intense yellow color obtained from residual fibers of juice processing. Although CAE is known to be rich in carotenoids and anacardic acids, the biological activities of this potential natural food colorant remain unexplored. The present study is the first to investigate the toxicity, antiproliferative and antimicrobial activities of the lyophilized CAE (L-CAE) and its encapsulated products, using maltodextrin (M-CAE) or cashew gum (CG-CAE) as carriers. In addition to their high carotenoid content, the phenolic contents in all materials was determined using UPLC-QTOF-MSE. The acute toxicity was performed using adult zebrafish (Danio rerio); antiproliferative activity was assessed using seven different human tumor cell lines [U-251 (glioblastoma), MCF-7 (breast, adenocarcinoma), NCI-ADR/RES (multidrug-resistant ovarian adenocarcinoma), NCI-H-460 (lung, large cell carcinoma), PC-3 (prostate, adenocarcinoma), OVCAR-3 (ovarian adenocarcinoma), and HT-29 (colon, adenocarcinoma)] and an immortalized human keratinocyte (HaCaT) while the antimicrobioal activity was evaluated on Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115, Escherichia coli ATCC 25922 and Salmonella Typhimurium ATCC 51812 microorganisms. Both lyophilized and encapsulated CAE samples did not exert acute toxicity against zebrafish neither antiproliferative effect against human tumor and non-tumor cell lines. Further, L-CAE showed potential antimicrobial activity against Listeria monocytogenes, which was confirmed using electron microscopy. The current findings demonstrated that CAE is a potential source of bioactive compounds to use as an additive in the food industry. [ABSTRACT FROM AUTHOR]

A [2+2]-cycloaddition of bis-isatin Schiff bases 5a–b and 7 with activated aryloxyacetic acid derivatives 8a–d afforded bis-spiroisatino β-lactams with aliphatic and aromatic spacers. The structures of the synthesized 2-oxindoles and spirooxindoles were determined based on Fourier-transform infrared spectroscopy, proton-1 and carbon-13 nuclear magnetic resonance spectroscopies and CHN analysis. Our interest in these bis-Schiff bases and bis-spiroisatino β-lactams is for their potential anticancer capabilities. In vitro bioactivity testing against the cervical adenocarcinoma (HeLa) and breast cancer (MCF-7) cell lines as well as noncancerous NIH/3T3 fibroblast cell was investigated applying the MTT assay. Bis-isatin derivatives 5a, 5b, 9h, 10a, and 10b showed promising antiproliferative activity toward these two cancer cell lines. Two of the bis-isatin Schiff bases, 5a and 5b, displayed IC50 values less than that of the clinically-used anticancer agent cisplatin towards both the MCF-7 and HeLa cells, while several of the bis-isatin β-lactams showed similar bioactivity to that of cisplatin. All of the oxindoles and spirooxindoles displayed a selective anticancer effect except 10b. To study the possible mechanism for this bioactivity, DNA and BSA binding analyses were performed using fluorescence and UV–visible spectroscopic techniques. The isatin adducts displayed excellent interaction propensity to CT-DNA as well as BSA. Molecular docking investigation carried out on DNA and BSA with promising molecules to show the possible mechanism of cytotoxicity activities. [ABSTRACT FROM AUTHOR]

New O-alkylaminoethylated derivatives of 3-hydroximinocholestene were synthesised and studied for in vitro cytotoxic effects. The obtained oily oxime ethers were solidified by preparing their oxalate salts. The steroidal compounds were screened against 60 human cancer cell lines at 10 μM. The study indicated that the compounds display selective cytotoxicity against leukemia cell lines. Dimethylamine (7a) and pyrrolidine (7d) derived O-alkylated steroidal oxalates displayed percent growth inhibition of 73.36%and 69.97 %, respectively, against CCRF-CEM leukemia cancer cell line. Partition coefficient values of the new steroids were also estimated to study the correlation of lipophilicity with the biological activity. The overall percentage growth inhibition of leukemia cell lines was 42% and 41% when treated with compounds 7a and 7d, respectively. Results obtained in the present study would help developing potent cytotoxic compounds with specificity toward leukemia cancer. [ABSTRACT FROM AUTHOR]

Natural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound 3d showed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS·+ was 2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products 2a, 2c, and 2e against cervix line HeLa, with 50% growth inhibition (GI50) of 5.6, 15.0, and 17.0 μM, respectively. All synthesized compounds presented varying degrees of response, some of them with similar results compared with the positive control 5-fluorouracil. AChE inhibition of the products was not as strong as the positive control galantamine; the most potent compound was 2e with a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by 2a (0.0902 mM). No inhibition in the evaluated concentrations was observed for products 2d and 3a-d. Docking of 2a and 2e was realized against AChE in order to gain insight into the interactions made between them and the enzyme residues in its catalytic gorge. In silico calculations for all synthesized products showed their drug-like properties. Alcohol derivatives, specially 2a and 2e, could be further derivatized in the search for new and improved drugs. [ABSTRACT FROM AUTHOR]

N-Alkyl-2-(substitutedbenzamido) benzamides and methyl 2-(2-(substitutedbenzamido) benzamido) alkanoates were prepared by either the reaction of amines or amino acid esters with benzoxazine derivatives or the DCC coupling of 2-substitutedbenzamido benzoic acid with amines or amino acid esters. Methyl 2-(2-(4-chlorobenzamido)benzamido alkanoates were used as the key intermediate for the preparation of dipeptide-coupled benzamides via azide and DCC coupling methods. The investigated compounds were subjected to in silico molecular docking as agonist for human σ1 receptor through their binding energies and analysis of ligand–receptor interactions and prediction study to their physicochemical properties and drug-likeness scores. Moreover, compounds with the highest binding affinity toward the target were screened against breast MCF-7 and liver A549 cancer cell lines to test their cytotoxic activities. Compounds 11a, 3a, 8c, 12a and 13b showed potent cytotoxic activity for the tested compounds against MCF-7 cell line with low IC50 values, especially for 11a (5.3 µM compared to the standard drug 5-FU 5.8 µM). Based on the identification of this hit candidate, new potent σ1 receptor with anti-cancer activity could be designed. [ABSTRACT FROM AUTHOR]

N-methyl-d-aspartate (NMDA) receptors, which are widely present in the central nervous system, have also been found to be up-regulated in a variety of cancer cells and tumors and they can play active roles in cancer cell growth regulation. NMDA receptor antagonists have been found to affect cancer cell viability and interfere with tumor growth. Moreover, cancer cells also have been shown to have elevated levels of some d-amino acids. Two human skin cell lines: Hs 895.T skin cancer and Hs 895.Sk skin normal cells were investigated. They were derived from the same patient to provide tumor and normal counterparts for comparative studies. The expression of specific NMDA receptors was confirmed for the first time in both skin cell lines. Dizocilpine (MK-801) and memantine, NMDA receptor channel blockers, were found to inhibit the growth of human skin cells by reducing or stopping NMDA receptor activity. Addition of d-Ser, d-Ala, or d-Asp, however, significantly reversed the antiproliferative effect on the human skin cells triggered by MK-801 or memantine. Even more interesting was the finding that the specific intracellular composition of a few relatively uncommon amino acids was selectively elevated in skin cancer cells when exposed to MK-801. It appears that a few specific and upregulated d-amino acids can reverse the drug-induced antiproliferative effect in skin cancer cells via the reactivation of NMDA receptors. This study provides a possible innovative anticancer therapy by acting on the d-amino acid pathway in cancer cells either blocking or activating their regulatory enzymes. [ABSTRACT FROM AUTHOR]

The current study was performed to evaluate the antiproliferative and apoptosis-inducing potential of n-hexane fraction from Cassia fistula L. (Caesalpinioideae) fruits. The antiproliferative property of the fraction was determined by MTT assay against cancer cell lines including HeLa, MG-63, IMR-32, and PC-3 with GI50 value of 97.69, 155.2, 143, and 160.2 μg/ml respectively. The fraction was further explored for its apoptotic effect using confocal, SEM, and flow cytometry studies in HeLa cells. It was observed that the treatment of fraction revealed fragmentation of DNA, chromatin condensation, membrane blebbing, and formation of apoptotic bodies in a dose-dependent manner. The fraction also showed a remarkable increase in the level of ROS, mitochondrial depolarization and G0/G1 phase cell cycle arrest, and induction in the phosphatidylserine externalization analyzed using Annexin V-FITC/PI double staining assay in HeLa cells. Kaempferol, Ellagic acid, and Epicatechin are the major phytoconstituents present in the fraction as revealed by the HPLC. The treatment of n-hexane fraction showed downregulation in the gene expression of Bcl-2 and upregulation in the expression level of p53, Bad, and caspase-3 genes analyzed using semi-quantitative RT-PCR in HeLa cells. These results suggest that n-hexane fraction from C. fistula inhibited the proliferation of cervical cancer cells efficiently by the induction of apoptosis. [ABSTRACT FROM AUTHOR]

The elevated blood sugar slowly attacks reactive amino group of functional proteins and impairs its functions, generates reactive oxygen species (ROS) as byproduct and increases risk of cancer. Bioactive peptides might act as protecting agent via trapping excess sugar. In this study, the bioactivity of peptides from Vicia faba by tryptic digestion was evaluated as antiglycation, antioxidant and antiproliferative assays. Results obtained indicated that V. faba peptides fractions < 3 kDa trapped extra glucose and fructose, inhibited in vitro glycation up to 49.5%, protected bovine serum albumin from glycation induced fibril formation, neutralized DPPH free radical and exhibited a cytotoxic effect against PC3, MCF-7 and HepG2 cell lines with a significant decrease in cell viability after 48 h of incubation (IC50 0.54 mg/ml to 7.58 mg/ml). Vicia faba peptides promising consumed as nutritional supplements due to its effective biological protection against diabetic complications and anticancer agent. Peptides obtained from Vicia faba were tested as antiglycation, antioxidants and antitumor activity against different cell lines. Different techniques and methods used including separation and identification of peptides from V. faba, peptides reactivity with reducing sugars, measuring peptides, measuring free sugars, antiglycation activity, MTT assay, DPPH radical assay and anti-proliferative effect of obtained peptides. Vicia faba could have the potential use as food ingredients or nutritional supplements due to its encapsulation of bioactive peptides. [ABSTRACT FROM AUTHOR]

Since the World Health Organization has suggested the exploration of natural products for cancer management owing to the side effects of chemotherapy and irradiation on humans and breast cancer accounts for the highest number of cancer related deaths globally, this study has examined antiproliferative effects of the aqueous and methanol extracts of Hypsizygus tessellatus (brown and white var.) and Flammulina velutipes caps against two breast cancer cell lines. The antioxidant and antiproliferative activities of these mushroom extracts were evaluated in vitro using chemical-based (for antioxidant activity) and cell (for antiproliferative activity) approaches. Furthermore, the phytochemical composition of the mushroom extracts were identified using mass spectroscopy (UPLC-QTOF/MS). The obtained results showed aqueous extracts of F. velutipes (Enoki) and white H. tessellatus (Bunapi shimeji) caps to possess higher antiodixant activities against DPPH (IC50 = 0.202 and 0.573 mg/mL, respectively), and H2O2 (IC50 = 0.622 and 0.745 mg/mL, respectively) compared tothe methanol extracts. Aqueous extracts of the mushrooms also showed better ferric reducing antioxidant power (FRAP) values against ferric ions compared to the methanol extracts. Finally, the mushroom extracts showed good antiproliferative activities against human breast cancer cell lines. These findings suggest the presence of phytochemicals with antiproliferative and antioxidant acrtivities in the mushroom extracts studied. [ABSTRACT FROM AUTHOR]

A series of new 3-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazole-4-carbaldehydes 4(a–g) and their benzimidazole derivatives 6(a–g) were synthesized under both conventional and microwave irradiation methods. However, we successfully achieved good yields in shorter reaction times under microwave irradiation. All the synthesized scaffolds were characterized by 1H NMR, 13C NMR, IR and mass spectral analyses. The synthesized compounds have been evaluated as potential antiproliferative agents. The antiproliferative activity of the synthesized compounds was studied against two cancer cell lines C6 (nerve cells) and MCF-7 (human breast adenocarcinoma cells) and among them, compounds 4g and 6b exhibited highly potent activity against C6 cell line and 6b–c exhibited highly potent activity against MCF-7 cell line. [ABSTRACT FROM AUTHOR]

An endophytic fungus Aspergillus fumigatus isolated from Moringa oleifera has been evaluated for its various bioactivities. The chloroformic fungal extract exhibited a good antimicrobial as well as antibiofilm activity against various pathogenic microorganisms. It also demonstrated a good antimutagenicity against the reactive carcinogenic ester generating mutagen, 2-aminofluorene (2-AF) with IC50 values of 0.52 mg ml−1 and 0.36 mg ml−1 in case of co-incubation and pre-incubation, respectively. The antiprolifertive activity against different cancer cell lines; such as HCT-15, HeLa A549 and U87-MG showed the IC50 values of 0.061, 0.065 and 0.072 mg ml−1, respectively. The antioxidant activity of fungal extract has been assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethyl-benzthiazolin-6-sulfonicacid) (ABTS) methods with IC50 values of 40.07 µg and 54.28 µg, respectively. Total phenolics and flavonoid contents have been also determined. Ultra-high performance liquid chromatography (UPLC) of fungal extract revealed the presence of various phenolic compounds (caffeic acid, rutin, ellagic acid, quercetin and kaempferol). Further an attempt has been made to purify the bioactive compounds by column chromatography and GC–MS analysis. The above studies demonstrated a good bioactive potential of endophytic fungus Aspergillus fumigatus and shows the pharmacological importance of an endophytic fungus and justify the need to carry out further studies. [ABSTRACT FROM AUTHOR]

The present study evaluated the potential biological activities of rhizospheric fungi isolated from the Achanakmar Biosphere Reserve, India. Fungus, Talaromyces purpureogenus isolate-ABRF2 from the soil of the Achanakmar biosphere was characterized by using morphological, biochemical and molecular techniques. Fungus was screened for the production of secondary metabolites using a specific medium. The metabolites were extracted using a suitable solvent and each fraction was subsequently evaluated for their antioxidant, antimicrobial, antiproliferative and anti-aging properties. The ethanolic extract depicted the highest antioxidant activity with 83%, 79%, 80% and 74% as assessed by ferric reducing power, 2,2-diphenyl 1-picrylhydrazyl, 2,2′-azino-bis3-ethylbenzthiazoline-6-sulfonic and phosphomolybdenum assays, respectively. Similarly, ethanolic extracts depicted marked antimicrobial activity as compared with standard antibiotics and antifungal agents as well as demonstrated significant antiproliferative property against a panel of mammalian cancer cell lines. Furthermore, different fractions of the purified ethanolic extract obtained using adsorption column chromatography were evaluated for antiproliferative property and identification of an active metabolite in the purified fraction using gas chromatography–mass spectroscopy and nuclear magnetic resonance techniques yielded 3-methyl-4-oxo-pentanoic acid. Thus, the present study suggests that the active metabolite 3-methyl-4-oxo-pentanoic acid extracted from Talaromyces purpureogenus isolate-ABRF2 has a potential antiproliferative, anti-aging, and antimicrobial therapeutic properties that will be further evaluated using in vivo studies in future. [ABSTRACT FROM AUTHOR]

Six zinc(II) complexes, [Zn(OCOPh)2LR] (R = 1, 2, 3, 4, 5, 6) were synthesized by the reaction of zinc benzoate and six para-substituted 4-phenyl-terpyridine complexes and their structures were confirmed by elemental analysis, FT-IR, 1H NMR and X-ray single crystal diffraction analysis. Their photoluminescent properties in solid and in solutions of DMSO were studied. Three human cancer cell lines were used for antiproliferative potential: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109) and human breast cancer cell line (MCF-7). The results have shown that these zinc complexes have good inhibitory effects on cancer cells, which are better than that of the commonly used clinical drug cisplatin. The ability of the complexes to binding to CT-DNA was studied by UV spectroscopy and fluorescence titration, while the interaction between the complexes and CT-DNA, AT6, GC6 short-chain DNA sequences and G-quadruplex were analyzed by circular dichroism (CD). It is found that these complexes can bind to DNA, and the binding mode is mainly intercalator. The docking of the complexes with the DNA fragment was simulated using molecular docking software. All the results clearly display that the substituents at these ligands of the complexes have the substitution effects on the properties of photoluminescence, antiproliferative potential and DNA binding study. [ABSTRACT FROM AUTHOR]

Halophytic plants growing in harsh desert environments are rich reservoirs of unique endophytic microorganisms. Here, healthy fresh plants of the families Tamaricaceae and Amarantaceae at three saline locations in Iran were investigated for their bioactive endophytic fungi. Among a vast number of isolates, eight isolates were identified as Humicola fuscoatra (Sordariomycetes, Pezizomycotina, Ascomycota) by microscopy and representative DNA sequences of the 5.8S rDNA (ITS) and partial β-tubulin (TUB2). Those isolates were halotolerant, and highly bioactive, so that their intra- and extra-cellular metabolites possessed in vitro antifungal, antibacterial and antiproliferative activities, against a number of fungal and bacterial plant pathogens including the fungi Arthrobotrys conoides, Pyrenophora graminea, Pyricularia grisea and the bacteria Agrobacterium tumefaciens, Pseudomonas syringae and Xanthomonas oryzae. Chemical analyses of metabolites from the endophytes using HNMR, CNMR, NOESY, COSY, HMBC, HSQC, DEPT, TOCSY and EI MASS techniques identified 3,8-dihydroxy-1-methyl-9,10-anthracenedione (aloesaponarin II; an anthraquinone derivative), 1,8,9-anthracenetriol structure (chrysarobin; an anthranol derivative) and 2,4-di-tert-butylthiophenol in fungal extracts. To the best of our knowledge, this is the first report of endophytic association of halotolerant H. fuscoatra isolates with Tamaricaceae and Amarantaceae, and their bioactivity against plant pathogens. Also, the capability of chrysarobin and aloesaponarin II production is new to the fungal kingdom. These findings may find application in agriculture, pharmacology, and biotechnology. [ABSTRACT FROM AUTHOR]

Plumbagin (PLB) is a phytochemical being used for centuries in traditional medicines. Recently, its capacity to inhibit the development of human tumors has been observed, through the induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis and metastasis. Here we evaluated the mechanism of action of PLB in the kidney adenocarcinoma 786-O cell line, which are metabolizing cells important for toxicology studies. After the treatment with PLB, we observed increased apoptosis and cell cycle arrest in S and G2/M phases, starting at 5 µM. In addition, PLB was cytotoxic, genotoxic and induced loss of cell membrane integrity. Regarding gene expression, treatment with 7.5 µM PLB reduced the amount of MTOR, BCL2 and ATM transcripts, and increased CDKN1A (p21) transcripts. Phosphorylation levels of yH2AX was increased and MDM2 protein level was reduced following the treatment with PLB, demonstrating its genotoxic effect. Our results suggest that PLB acts in molecular pathways related to the control of proliferation and cell death in 786-O cells. [ABSTRACT FROM AUTHOR]