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Abstract Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide and has a poor prognosis in black Africans. Traditional herbal practitioners in southwestern Nigeria use Crinum jagus (J. Thompson) Dandy for cancer treatment. This study screens methanol and ethyl acetate extracts of C. jagus leaves for activity against hepatocellular carcinoma (HepG2) cell line using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The antiproliferative properties of the extracts were assessed by comparing their IC50 values with that of the standard drug, cisplatin. The GC–MS technique was used to identify the phytoconstituents in the extracts. The drug-likeness of each identified phytoconstituents in the extracts was determined by following Lipinski’s rule of five. In addition, phytoconstituents having drug-like properties were screened as potential inhibitors of the p53–mortalin interaction by docking them against the mortalin residues 3N8E and 4KBO using Swissdock. Results For the antiproliferative study, the IC50 values obtained for cisplatin, methanol, and ethyl acetate extracts of leaves were 5 µg/mL, 5 µg/mL, and 70 µg/mL, respectively, indicating that the methanol extract and cisplatin possess comparable antiproliferative properties. Hexadecanoic acid, hexadecanoic acid methyl ester, tangeretin, galanthamine, and crinamine, which were part of the constituents identified in the leaves, possess drug-like properties and are known to show cytotoxic properties against several cancer cell lines. On docking with mortalin residue 3N8E, hexadecanoic acid and hexadecanoic acid methyl ester had comparable binding energy (− 8.21 kcal mol−1) with withaferin A and withanone (8.29 kcal mol−1 and 8.14 kcal mol−1). Hexadecanoic acid, hexadecanoic acid methyl ester, and galanthamine had binding energy of − 7.66, − 7.45, and − 7.47 kcal mol−1, respectively, with mortalin residue, 4KBO, comparable to values of − 7.68 and − 7.59 kcal mol−1 obtained for withaferin A and withanone, respectively. Conclusion The methanol extract of C. jagus leaves demonstrated remarkable antiproliferative activities against HepG2, justifying its use in traditional medicine for cancer treatment. The ethyl acetate and methanol extracts contain drug-like compounds with known cytotoxic properties against several cancer cell lines. Some of these compounds (hexadecanoic acid, hexadecanoic acid methyl ester, tangeretin, and galanthamine) are inhibitors of the p53–mortalin interaction. Graphical Abstract

Indole phytoalexins, found in economically significant Cruciferae family plants, are synthesized in response to pathogen attacks or stress, serving as crucial components of plant defense mechanisms against bacterial and fungal infections. Furthermore, recent research indicates that these compounds hold promise for improving human health, particularly in terms of potential anticancer effects that have been observed in various studies. Since our last comprehensive overview in 2016 focusing on the antiproliferative effects of these substances, brassinin and camalexin have been the most extensively studied. This review analyses the multifaceted pharmacological effects of brassinin and camalexin, highlighting their anticancer potential. In this article, we also provide an overview of the antiproliferative activity of new synthetic analogs of indole phytoalexins, which were synthesized and tested at our university with the aim of enhancing efficacy compared to the parent compound.

Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 μM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 μM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.

Plant polysaccharides have gained interest in medical research for their ability to suppress various diseases, including cancer. However, information on some plant polysaccharides is yet to be uncovered. In this study, we screened crude polysaccharides extracted from six different plants for their antioxidative and antiproliferative activities. Crude polysaccharides were isolated from different parts of some plants using the established extraction protocol. The crude polysaccharides were evaluated for their chemical composition (protein, total sugar, and phenolics), free radical-scavenging activities, and antiproliferative activities against breast cancer MCF-7 cells as well as non-cancerous cells, i.e., human fibroblast MRC-5 cells and Cercopithecus aethiops kidney Vero cells, via an MTT assay and CM20 Incubation Monitoring System (Olympus) for MCF-7. The investigated crude polysaccharides showed significant variations in their chemical constituents and antioxidative properties. Only Moringa seed crude polysaccharide extracts showed significant antiproliferative activities at various concentrations, with an IC50 value of 0.061 mg/mL, which was about 2.6 folds higher on MRC-5 and Vero cell lines. The antiproliferative activities toward cancer cell lines and lack of significant toxicity in the case of normal cells indicate that this extract may be promising as a valuable source for novel cancer therapy.

Bisindole alkaloids are a source of inspiration for the design and discovery of new-generation anticancer agents. In this study, we investigated the cytotoxic and antiproliferative activities of three spirobisindole alkaloids from the traditional anticancer Philippine medicinal plant Voacanga globosa, along with their mechanisms of action. Thus, the alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) showed in vitro cytotoxicity and antiproliferative activities against the tested cell lines (L929, KB3.1, A431, MCF-7, A549, PC-3, and SKOV-3) using MTT and CellTiter-Blue assays. Globospiramine (1) was also screened against a panel of breast cancer cell lines using the sulforhodamine B (SRB) assay and showed moderate cytotoxicity. It also promoted the activation of apoptotic effector caspases 3 and 7 using Caspase–Glo 3/7 and CellEvent-3/7 apoptosis assays. Increased expressions of cleaved caspase 3 and PARP in A549 cells treated with 1 were also observed. Apoptotic activity was also confirmed when globospiramine (1) failed to promote the rapid loss of membrane integrity according to the HeLa cell membrane permeability assay. Network pharmacology analysis, molecular docking, and molecular dynamics simulations identified MAPK14 (p38α), a pharmacological target leading to cancer cell apoptosis, as a putative target. Low toxicity risks and favorable drug-likeness were also predicted for 1. Overall, our study demonstrated the anticancer potentials and apoptotic mechanisms of globospiramine (1), validating the traditional medicinal use of Voacanga globosa.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant’s methanolic root extract (BVR) against colon cancer cells. Studies were conducted in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3, 46.1, and 50.2 µg/mL for the LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of the cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. Nuclear double staining revealed the great proapoptotic BVR properties in HT-29 cells and subtle effect in LS180 cells. RT-qPCR with the relative quantification method showed significant changes in the expression of genes related to apoptosis in both the LS180 and HT-29 cells. The genes BCL2L1 (126.86–421.43%), BCL2L2 (240–286.02%), CASP3 (177.19–247.83%), and CASP9 (157.99–243.75%) had a significantly elevated expression, while BCL2 (25–52.03%) had a reduced expression compared to the untreated control. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93 ± 0.01, 122.92 ± 0.01, and 220.29 ± 0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+, and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62.60 ± 0.87% of enzyme inhibition. The chemical composition of BVR was determined using a UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). The results are very promising and encourage the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer, and were widely discussed alongside data from the literature.

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

Ovarian cancer, a highly lethal malignancy among reproductive organ cancers, poses a significant challenge with its high mortality rate, particularly in advanced-stage cases resistant to platinum-based chemotherapy. This study explores the potential therapeutic efficacy of 1-methoxyisobrassinin (MB-591), a derivative of indole phytoalexins found in Cruciferae family plants, on both cisplatin-sensitive (A2780) and cisplatin-resistant ovarian cancer cells (A2780 cis). The findings reveal that MB-591 exhibits an antiproliferative effect on both cell lines, with significantly increased potency against cisplatin-sensitive cells. The substance induces alterations in the distribution of the cell cycle, particularly in the S and G2/M phases, accompanied by changes in key regulatory proteins. Moreover, MB-591 triggers apoptosis in both cell lines, involving caspase-9 cleavage, PARP cleavage induction, and DNA damage, accompanied by the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. Notably, the substance selectively induces autophagy in cisplatin-resistant cells, suggesting potential targeted therapeutic applications. The study further explores the interplay between MB-591 and antioxidant N-acetylcysteine (NAC), in modulating cellular processes. NAC demonstrates a protective effect against MB-591-induced cytotoxicity, affecting cell cycle distribution and apoptosis-related proteins. Additionally, NAC exhibits inhibitory effects on autophagy initiation in cisplatin-resistant cells, suggesting its potential role in overcoming resistance mechanisms.

The aim of this work is to describe the effect of convective drying (CD), vacuum drying (VD), infrared drying (IRD), low-temperature vacuum drying (LTVD) and freeze drying (FD) on bio-compound retention of red cabbage and its beneficial health properties. The total phenolics content (TPC), flavonoids (TFC), anthocyanin (TAC) and glucosinolates (TGC) were determined by spectrophotometry. The profiles of phenolic acids, amino acids and fatty acids were determined by HPLC-UV-DAD, LC-DAD and GC-FID, respectively. Antioxidant potential was verified by DPPH and ORAC assays. The antiproliferative activity was measured in the human gastric cell line (AGS). Anti-inflammatory activity was evaluated by phorbol 12-myristate 13-acetate and arachidonic acid models. VD showed high values of TPC = 11.89 ± 0.28 mg GAE/g d.m.; TFC = 11.30 ± 0.9 mg QE/g d.m.; TAC = 0.265 ± 0.01 mg Cya3glu/g d.m.; and TGC = 51.15 ± 3.31 µmol SE/g d.m. Caffeic acid, ferulic acid and sinapic acid were identified. The predominant amino acid and fatty acid were glutamic acid and γ–linolenic acid, respectively. The antioxidant potential was dependent on drying methods for both DPPH and ORAC assays. Dried red cabbage extracts showed clear anti-inflammatory and antiproliferative activity. The dehydration process is an alternative for the retention of bio-compounds and health-promoting properties of red cabbage.

Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2–8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable antifungal and antibacterial efficacy. The synthesized derivatives showed minimum inhibitory concentration (MIC) values ranging from 0.75 µg/mL to 1.50 µg/mL and minimum bactericidal concentrations (MBCs) ranging from 8.00 µg/mL to 16.00 µg/mL. Compound 6 inhibited Ehrlich ascites carcinoma (EAC) cell proliferation by 10.36% with an IC50 of 2602.23 μg/mL in the MTT colorimetric assay. The obtained results were further rationalized by docking analysis of the synthesized derivatives against 4URO and 4XE3 receptors to explore the binding affinities and nonbonding interactions of MGP derivatives with target proteins. Compound 6 demonstrated the potential to bind with the target with the highest binding energy. In a stimulating environment, a molecular dynamics study showed that MGP derivatives have a stable conformation and binding pattern. The MGP derivatives were examined using POM (Petra/Osiris/Molinspiration) bioinformatics, and as a result, these derivatives showed good toxicity, bioavailability, and pharmacokinetics. Various antifungal/antiviral pharmacophore (Oδ−, O′δ−) sites were identified by using POM investigations, and compound 6 was further tested against other pathogenic fungi and viruses, such as Micron and Delta mutants of SARS-CoV-2.

Abstract Curcumin, the primary polyphenol found in turmeric, is derived from the Curcuma longa plant. Since curcumin is nontoxic and has a wide range of medicinal qualities, including anti-oxidant, analgesic, anti-inflammatory, and antibacterial action, it has been widely employed in Ayurveda medicine for ages. Curcumin has recently been discovered to have anti-cancer properties through its impact on numerous biological pathways involved in carcinogenesis, metastasis, tumorigenesis, cell cycle regulation, mutagenesis, and oncogene expression. In this study, we determined the Antiproliferative activity and apoptosis-inducing mechanism of C. longa (Turmimax®) on human cancer cells. The cytotoxic effect was evaluated against HeLa cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Flow cytometric analysis was performed to detect apoptotic cell death. Turmimax® exhibits promising properties as a potential anti-cancer therapeutic agent in human cervical adenocarcinomas and possibly other cancer types, with an IC50 value of 87.89 µg/mL. In HeLa cells treated with Turmimax®, cell cycle arrest was seen in the G0/G1 and S phases. By inducing apoptosis and increasing the number of apoptotic cells in a dose-dependent manner, the experimental data suggest that Turmimax® has considerable promise in cancer prevention and treatment.

trans-Anethole a valuable compound derived from star anise widely used by ethnic tribals to manage numerous human diseases. In this study antiproliferative activities of trans-Anethole towards human liver cancer (HepG2), cervical cancer (HeLa) and breast cancer (MCF-7) cells were explored. trans-Anethole showed free radical scavenging potential as assessed by DNA nicking assay. trans-Anethole exhibited strong antiproliferative potential towards HepG2 cells compared to other cell lines. trans-Anethole strongly induced apoptosis in HepG2 cells by significantly upregulating the protein expressions of p53, Caspase-3 and Caspase-9 were assessed by western blotting analysis which highlighted apoptosis-inducing capacity of trans-Anethole against HepG2 cells. Rt-qPCR analysis revealed that trans- Anethole upregulated p53, caspase − 3 and − 9 in comparison to untreated HepG2 cancer cells. Moreover, trans-Anethole provoked the generation of ROS and disruption of MMP. Our research suggests that trans-Anethole may have a significant anticancer therapeutic potential for treating liver cancer.

Prostate cancer remains one of the leading health issues without a fully effective treatment. Medicinal plants are one of the primary sources of compounds for treating numerous ailments. In this sense, the Oenothera genus contains metabolites with antiproliferative activity on cancer cells. For this, the study aimed to explore the antiproliferative activity of its extracts against prostate cancer and identify its metabolites (under metabolomics analyses) associated with anticancer and/or antiproliferative properties. For this reason, a LC-MS/MS-based metabolomic analysis was performed to demonstrate the possible metabolites present in O. rosea. In addition, the antiproliferative activity of different extracts in the human prostate cancer cell line DU145 was evaluated. All extracts have antiproliferative effects on DU145 cells at 72 h, with moderate activity being the best ethanolic either 48 or 72 h. Finally, by LC-MS/MS-based metabolomics, 307 compounds from aqueous, methanolic, ethanolic, and ethyl acetate extracts from which 40 putative metabolites identified were organized as anti-inflammatory, anticancer, and/or antiproliferative activities according to previously reported. These results provide evidence that O. rosea could be used as an antiproliferative agent due to its chemical contents used as polypharmacy with low concentration levels.

A new series of 4‐benzyl analogues of 1,2,4‐benzothiadiazine‐1,1‐dioxide was synthesized. All these compounds were subsequently tested for in vitro anti‐cancer activity against cancer cell lines selected by National Cancer Institute using one dose (10−5 M), following their standard screening procedure. The new compounds were characterized by 1H NMR, 13C NMR, LCMS, and IR techniques. All the synthesized compounds showed sensitivity against tested cancer cell lines. Notably, the compound having 3‐fluoro‐4‐methoxybenzyl group on 1,2,4‐benzothiadiazine‐1,1‐dioxide ring exhibited the most promising cytotoxicity effect. It displayed a growth percentage oscillating between −32.82 % and 93.85 % on Melanoma and Breast cancer cell lines, respectively. Additionally, this compound demonstrated a significant antiproliferative effect on Leukaemia and CNS cancer cell lines. The most affected cell lines were MDA‐MB‐468 (Breast Cancer, lethality is 32.82 %) and MDA‐MB‐435 (Melanoma, −15.62 %). Other compounds in the series also demonstrated considerable antiproliferative effects on Breast cancer cell line. [ABSTRACT FROM AUTHOR]

Syntheses of five (1–5) cationic organometallic complexes bearing two platinum (II) centers are being reported. Compounds 1 and 2 have a flexible molecular backbone and are isomeric. Compounds 3, 4, and 5 are structural isomers with a rigid structural framework and containing pyrimidine/pyrazine in the center and two pendant arms bearing the alkynyl–ditopic platinum units. Compounds 1–5 were systematically characterized using FT‐IR, NMR [1H, 31P{1H}, and 13C{1H}], and HRMS. The antiproliferative activity of these compounds was examined against HeLa cancer cell line, and results were compared with that of cisplatin. "Live/dead" cell death assay was performed to ratify the superior antiproliferative activities of some of these organometallic complexes with respect to cisplatin. [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]

Dendrobium loddigesii has long been used in traditional folk medicine. The purpose of this study was to optimize the culture conditions for its protocorm-like bodies (PLBs) and explore their biological activities. The use of an air-lift bioreactor demonstrated superior PLB proliferation compared to agitated and solid culture methods. The optimal inoculum quantity of 30 g/vessel, cultured for 28 days in the bioreactor, yielded the highest PLB biomass production. Analysis of PLB extracts revealed that the ethyl acetate (EtOAc) extract exhibited the highest levels of flavonoids and alkaloids, as well as potent antioxidant activity demonstrated by DPPH free radical scavenging assay and reducing power. Furthermore, the antiproliferative effects of the PLB extracts were assessed using MTT assays, and the EtOAc extract showed significant efficacy by reducing cell viability by over 60% in the human colon carcinoma cell line SW620 at the highest tested concentration (200 μg/mL). Mechanistic analysis revealed the downregulation of key regulatory apoptosis genes, including survivin, p53, caspase-3, and caspase-9. These results demonstrate the potential of the bioreactor culture method for the efficient production of D. loddigesii PLBs and the biological activities of the EtOAc extract, suggesting its therapeutic potential. [ABSTRACT FROM AUTHOR]

A small set of indole-based derivatives, IV and Va–I, was designed and synthesized. Compounds Va–i demonstrated promising antiproliferative activity, with GI50 values ranging from 26 nM to 86 nM compared to erlotinib's 33 nM. The most potent antiproliferative derivatives—Va, Ve, Vf, Vg, and Vh—were tested for EGFR inhibitory activity. Compound Va demonstrated the highest inhibitory activity against EGFR with an IC50 value of 71 ± 06 nM, which is higher than the reference erlotinib (IC50 = 80 ± 05 nM). Compounds Va, Ve, Vf, Vg, and Vh were further tested for BRAFV600E inhibitory activity. The tested compounds inhibited BRAFV600E with IC50 values ranging from 77 nM to 107 nM compared to erlotinib's IC50 value of 60 nM. The inhibitory activity of compounds Va, Ve, Vf, Vg, and Vh against VEGFR-2 was also determined. Finally, in silico docking experiments attempted to investigate the binding mode of compounds within the active sites of EGFR, BRAFV600E, and VEGFR-2. [ABSTRACT FROM AUTHOR]

2,3,4-trisubstituted thiazoles 3a–i, having a methyl group in position four, were synthesized by the reaction of 1,4-disubstituted thiosemicarbazides with chloroacetone in ethyl acetate/Et3N at room temperature or in ethanol under reflux. The structures of new compounds were determined using NMR spectroscopy, mass spectrometry, and elemental analyses. Moreover, the structure of compound 3a was unambiguously confirmed with X-ray analysis. The cell viability assay of 3a–i at 50 µM was greater than 87%, and none of the tested substances were cytotoxic. Compounds 3a–i demonstrated good antiproliferative activity, with GI50 values ranging from 37 to 86 nM against the four tested human cancer cell lines, compared to the reference erlotinib, which had a GI50 value of 33 nM. The most potent derivatives were found to be compounds 3a, 3c, 3d, and 3f, with GI50 values ranging from 37 nM to 54 nM. The EGFR-TK and BRAFV600E inhibitory assays' results matched the antiproliferative assay's results, with the most potent derivatives, as antiproliferative agents, also being the most potent EGFR and BRAFV600E inhibitors. The docking computations were employed to investigate the docking modes and scores of compounds 3a, 3c, 3d, and 3f toward BRAFV600E and EGFR. Docking computations demonstrated the good affinity of compound 3f against BRAFV600E and EGFR, with values of −8.7 and −8.5 kcal/mol, respectively. [ABSTRACT FROM AUTHOR]

Since lung cancer is the leading cause of cancer-related death worldwide, research is being conducted to discover anticancer agents as its treatment. Eleutherine bulbosa, a Dayak folklore medicine, exhibited anticancer effects against several cancer cells; however, its anticancer potency against lung cancer cells has not been explored yet. This study aims to determine the anticancer potency of E. bulbosa bulbs against lung cancer cells (A549) using 2D and 3D culture models, as well as determine its active compounds using gas chromatography-mass spectrometry (GC-MS) analysis. Three fractions of E. bulbosa bulbs, namely chloroform, n-hexane, and ethyl acetate, were tested for cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) and CellTiter-Glo. The antiproliferative effects of the most cytotoxic fraction against the 2D culture model were determined by a clonogenic survival assay and propidium iodide/Hoechst 33342 double staining, whereas the effects against the 3D culture model were determined by microscopy, flow cytometry, and gene expression analysis. The chloroform fraction is the most cytotoxic against A549 cells than other fractions, and it inhibited colony formation and induced apoptosis of A549 cells. The chloroform fraction also inhibited the growth of the A549 spheroid by suppressing the spheroid size, inducing apoptosis, reducing the proportion of CD44 lung cancer stem cells, causing arrest at the S phase of the cell cycle, and suppressing the expression of the SOX2 and MYC genes. Furthermore, the GC-MS analysis detected 20 active compounds in the chloroform fraction, including the major compounds of eleutherine and isoeleutherine. In conclusion, the chloroform fraction of E. bulbosa bulbs exhibit its antiproliferative effect on 2D and 3D culture models of A549 cells, suggesting it could be a lung cancer chemopreventive agent. [ABSTRACT FROM AUTHOR]

The present study aimed to characterize the antiproliferative and antimetastatic properties of two recently synthesized monoterpene-aminopyrimidine hybrids (1 and 2) on A2780 ovary cancer cells. Both agents exerted a more pronounced cell growth inhibitory action than the reference agent cisplatin, as determined by the MTT assay. Tumor selectivity was assessed using non-cancerous fibroblast cells. Hybrids 1 and 2 induced changes in cell morphology and membrane integrity in A2780 cells, as evidenced by Hoechst 33258–propidium iodide fluorescent staining. Cell cycle analysis by flow cytometry revealed substantial changes in the distribution of A2780 ovarian cancer cells, with an increased rate in the subG1 and G2/M phases, at the expense of the G1 cell population. Moreover, the tested molecules accelerated tubulin polymerization in a cell-free in vitro system. The antimetastatic properties of both tested compounds were investigated by wound healing and Boyden chamber assays after 24 and 48 h of incubation. Treatment with 1 and 2 resulted in time- and concentration-dependent inhibition of migration and invasion of A2780 cancer cells. These results support that the tested agents may be worth of further investigation as promising anticancer drug candidates. [ABSTRACT FROM AUTHOR]

Inhibition of the cyclin dependent kinase 2 (CDK2) is a well-known cancer treatment approach. Based on the molecular docking simulation analysis, two new series of 2-(1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethylidene)hydrazineylidene)-2,5-dihydrothiazole as CDK-2 inhibitors were designed. The lead compound IV (5-benzoyl-N2-phenyl-1,3-thiazole-2,4-diamine) was modified and optimized prior to this analysis. In contrast to Roniciclib (−8.6 kcal/mol), docking results of CDK2 hits showed high affinity and docking scores ranging from −9.1 to −10.3 kcal/mol. All of the compounds studied were evaluated in vitro for CDK2 inhibitory activity. In comparison to Roscovitine's IC50 of 0.432 µM, compound 11b had a maximum IC50 of 0.416 µM. Additionally, all hits were tested for antiproliferative activities against PC-3 human prostate cancer cells, HEPG-2 human hepatocellular carcinoma, and MCF-7 breast adenocarcinoma cell lines. The arylhydrazine moiety of the tested compounds 11a–e demonstrated high potency against HEPG-2, with 11b (IC50 = 0.11 µM) being more active than doxorubicin (IC50 = 0.12 µM). In addition, compound 11b (IC50 = 0.245 µM) was nearly as effective as doxorubicin (IC50 = 0.246 µM) against MCF-7 cancer cells. 11d showed superior antiproliferative activity against PC-3 cell line (IC50= 0.23 µM) relative to doxorubicin (IC50 = 0.29 µM). [ABSTRACT FROM AUTHOR]

Although crops produced in organic cultivation are considered to be better for health and often have better sensory characteristic than conventionally produced foodstuffs, the influence of cropping practice on phytochemicals content and healing properties of plant-based food still needs clarification. This study compared nutrient quality and biological activity of Brassica oleracea vegetables grown under organic and conventional production systems. Total glucosinolate, phenolics and flavonoids concentrations, together with antioxidant capacity of vegetable juices against 1,1-diphenyl-2-picryl-hydrazyl radicals (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and cupric ion reagent were estimated. Antimicrobial activity against bacteria and fungi, together with antiproliferative activity in tumour cell lines were investigated. Organic cropping increased total glucosinolates concentration in broccoli (B. oleracea L., var. italica Plenck) and cauliflower (B. oleracea L. var. botrytis l.c.). Higher total flavonoids concentration was found in all conventionally grown vegetables. Juices of conventionally grown broccoli and cauliflower were more effective antioxidants, antimicrobials and cancer chemopreventive agents than their organically grown counterparts and those from kohlrabi (B. oleracea L. var. gongylodes l.c). Cropping system and vegetable variety together affected chemical composition and biological activity of B. oleracea vegetables. Thus, the combination of both factors must be considered when producing vegetables with health-promoting properties. [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the most important treatment options in the treatment of all types of leukemia, but multi-drug resistance often precludes the success of this treatment. In this study, anticancer properties of heterocyclic salicylaldimines and their Cu(II) complexes on K562 human chronic myelogenous leukemia cell line were investigated. Doxorubicin was used as positive control. Compounds (C1-8 and doxorubicin) were placed to 96-well culture plate in triplicate order at doses of 1, 10, 100, 1000 µM and then K562 cells were seeded into the wells at the dose of 105/ml. After 72 h incubation, colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide test was performed to determine half-maximal inhibitory concentration values of each compound. Antiproliferative effects of compounds were determined using carboxyfluorescein succinimidyl ester assay. Apoptosis induction potential of each compound determined by mitochondrial membrane potential analysis (Rho123), cleaved caspase-3 expression analysis by flow cytometry and immunofluorescent staining and cell morphology analysis by giemza, hematoxylin and eosin and Papanicolaou protocols. The metal complexes of the compounds had stronger cytotoxic effects and cleaved caspase-3 expression than their ligands. Mitochondrial membrane potential was found at low levels in cells treated with Schiff base compounds and doxorubicin. In the cell morphology analyzes, chromatin condensation and marginalization, changes in the cell membrane, ghost cells and apoptotic bodies were observed as evidence of apoptosis formation. Among the tested heterocyclic Schiff base compounds, the powerful cytotoxic and apoptosis-inducing potential of Bis((9-((cycloheptylimino)methyl)-1,1,7,7-tetramethyl-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-yl)oxy)copper complex (C6) draws attention as a promising compounds withal a need for further in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to identify main phytocompounds and to evaluate the antiproliferative effect of the ethanolic extract of Apium graveolens seeds. Materials and Methods: in vitro antiproliferative study of A. graveolens ethanolic extract was investigated against MCF-7 cells breast cancer cell lines using the MTT colorimetric assay. Further, the main bioactive components were elucidated by Gas Chromatography-Mass Spectrometry (GC-MS). Commercial mass spectral library was used for the depiction of individual phytocomponents. Results: Terpenes were the main compounds found in the ethanolic extract of seeds of A. graveolens. In antiproliferative assay, the ethanolic extract in analysis showed significant activity in the proposed conditions. About six components were identified through GC-MS. This study showed the presence of different phytocomponents like Oleanane-3, 16-diol, 13, 28-epoxy-, diacetate, (3.beta., 16.alpha.) [Triterpenes]; Bacchotricuneatin C [Diterpene Lactone]; Cyclopropa[5,6]cholestane, 3-ethoxy-3',6-dihydro-, (3.alpha.,5.alpha.,6.beta.) [Phytosterol]; Fumaric acid, decyl 3-pentyl ester; Anthra[2,3-d]-1,3-dioxole-5,10-dione, 3a,4,11,11a-tetrahydro -9-hydroxy-7-methoxy-2,2,3a-trimethyl-, cis-[Glycoside]; Olean-12-en-28-oic acid, 3.beta.-hydroxy-21-oxo-, methyl ester [Triterpenes]. Conclusion: In-vitro cytotoxic activity of the ethanolic extract of the plant seeds has been evaluated and showed significant anti-proliferative effect against MCF-7 breast cancer cell lines. The study represents the first report of these compounds from Apium graveolens seeds ethanolic extract. [ABSTRACT FROM AUTHOR]

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFβ-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit. Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O2) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods. Results: In vitro, riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1β expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA. Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH. [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]

There is no doubt that significant progress has been made in tumor therapy in the past decades. However, the discovery of new molecules with potential antitumor properties still remains one of the most significant challenges in the field of anticancer therapy. Nature, especially plants, is a rich source of phytochemicals with pleiotropic biological activities. Among a plethora of phytochemicals, chalcones, the bioprecursors of flavonoid and isoflavonoids synthesis in higher plants, have attracted attention due to the broad spectrum of biological activities with potential clinical applications. Regarding the antiproliferative and anticancer effects of chalcones, multiple mechanisms of action including cell cycle arrest, induction of different forms of cell death and modulation of various signaling pathways have been documented. This review summarizes current knowledge related to mechanisms of antiproliferative and anticancer effects of natural chalcones in different types of malignancies including breast cancers, cancers of the gastrointestinal tract, lung cancers, renal and bladder cancers, and melanoma. [ABSTRACT FROM AUTHOR]

Plants belonging to the Fabaceae family have great importance in animal nutrition and the protection of human health (antidiabetic, anticarcinogenic, antioxidant, anti-inflammatory, and cardiovascular). Onobrychis, known as a potent antioxidant, anticarcinogenic and antimicrobial agent, its high phenolic substance is one of the important genera of this family. In this study, chloroform (OAC), ethanol (OAE), and water (OAW) extract of Onobrychis argyrea subsp. argyrea (O. argyrea) specie was prepared; and the antiproliferative, antimicrobial, and antioxidant activities were investigated. The antiproliferative effects of the extracts were evaluated on different cancer cell lines by XTT colourimetric method. OAE demonstrated the most excellent efficacy against all cell lines, according to the findings. MCF-7 83.71%, A549 92.14%, and HT-29 72.24% were all inhibited. The antimicrobial activity of OAE and OAW extracts against Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae was determined using the disc-diffusion technique. Finally, antioxidant power was determined using DPPH and FRAP methods. In the DPPH research, OAE and OAW extracts showed the highest levels of inhibition (IC50: 34.12±0.2 and 21.58±0.12, respectively). OAE (257.95±1.40) and OAW (282.14±0.83) extracts showed high activity with similar results in the FRAP method. Total phenolic content was determined as 226.15±1.89 mg GAE/g for OAE and 146.52±0.71 mg GAE/g for OAW, respectively. These results show that the species is an essential source of antioxidants. These studies are the first data for Onobrychis argyrea subsp. argyrea. All these results show that the plant has various biological activities and rich secondary metabolites. [ABSTRACT FROM AUTHOR]

Green algae are natural bioresources that have excellent bioactive potential, partly due to sulfated polysaccharides (SPs) which are still rarely explored for their biological activities. There is currently an urgent need for studies exploring the anticancer biological activity of SPs extracted from two Indonesian ulvophyte green algae: the sulfated polysaccharide of Caulerpa racemosa (SPCr) and the sulfated polysaccharide of Caulerpa lentillifera (SPCl). The method of isolating SPs and their assessment of biological activities in this study were based on previous and similar studies. The highest yield sulfate/total sugar ratio was presented by SPCr than that of SPCl. Overall, SPCr exhibits a strong antioxidant activity, as indicated by smaller EC50 values obtained from a series of antioxidant activity assays compared to the EC50 values of Trolox (control). As an anti-obesity and antidiabetic, the overall EC50 value of both SPs was close to the EC50 of the positive control (orlistat and acarbose). Even more interesting was that SPCl displayed wide-ranging anticancer effects on colorectal, hepatoma, breast cancer cell lines, and leukemia. Finally, this study reveals new insights in that SPs from two Indonesian green algae have the potential to be promising nutraceuticals as novel antioxidative actors, and to be able to fight obesity, diabetes, and even cancer. [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]

Background: Leaves, flowers and young shoots of yellow Camellia species are often used as a substitute for green tea in Vietnam. Yellow Camellia species contain high levels of polyphenol compounds, and have shown activities such as antioxidant, anticancer, and cytotoxic. Objectives: We qualitatively screened phytochemicals, quantified total polyphenols of 70% ethanol (EtOH) extracts of leaves, young shoots, and flowers of Camellia vuquangensis and Camellia hatinhensis in Ha Tinh Province, Vietnam. Furthermore, these extracts have been evaluated for lipid peroxidation inhibitory activities at the in vivo level in the BALB/c mouse model, and in vitro cytotoxic activities. Materials and Methods: Chemical methods and thin-layer chromatographic (TLC) analysis were used for the qualitative screening of phytochemicals. High-performance liquid chromatography (HPLC) was used to determine total polyphenols. Cell survival was determined through optical density (OD) measured when the protein composition of the cells was stained with sulforhodamine B (SRB). Inhibition of lipid peroxidation was evaluated by determining the content of malondialdehyde (MDA), which is a product of membrane lipid peroxidation. Results: The total polyphenol contents of all parts of the two species were comparable to that of green tea with values between 319.3 and 342.6 mg gallic acid equivalents (GAE/g) dry weight. Extracts of leaves, flowers of C. vuquangensis and C. hatinhensis showed strong lipid peroxidation inhibitory activities (IC50: 7.92–17.45 µg/mL) and moderate cytotoxic activities against cell lines HepG2, A549, MCF7, SK-Mel-2, HT-29, and AGS (IC50: 34.73–80.58 µg/mL). Conclusion: These two tea species may be considered as herbal teas with various health benefits. [ABSTRACT FROM AUTHOR]

The fraction of low-abundance microbiota in the marine environment is a promising target for discovering new bioactive molecules with pharmaceutical applications. Phenomena in the ocean such as diel vertical migration (DVM) and seasonal dynamic events influence the pattern of diversity of marine bacteria, conditioning the probability of isolation of uncultured bacteria. In this study, we report a new marine bacterium belonging to the rare biosphere, Leeuwenhoekiella parthenopeia sp. nov. Mr9T, which was isolated employing seasonal and diel sampling approaches. Its complete characterization, ecology, biosynthetic gene profiling of the whole genus Leeuwenhoekiella, and bioactivity of its extract on human cells are reported. The phylogenomic and microbial diversity studies demonstrated that this bacterium is a new and rare species, barely representing 0.0029% of the bacterial community in Mediterranean Sea metagenomes. The biosynthetic profiling of species of the genus Leeuwenhoekiella showed nine functionally related gene cluster families (GCF), none were associated with pathways responsible to produce known compounds or registered patents, therefore revealing its potential to synthesize novel bioactive compounds. In vitro screenings of L. parthenopeia Mr9T showed that the total lipid content (lipidome) of the cell membrane reduces the prostatic and brain tumor cell viability with a lower effect on normal cells. The lipidome consisted of sulfobacin A, WB 3559A, WB 3559B, docosenamide, topostin B-567, and unknown compounds. Therefore, the bioactivity could be attributed to any of these individual compounds or due to their synergistic effect. Beyond the rarity and biosynthetic potential of this bacterium, the importance and novelty of this study is the employment of sampling strategies based on ecological factors to reach the hidden microbiota, as well as the use of bacterial membrane constituents as potential novel therapeutics. Our findings open new perspectives on cultivation and the relationship between bacterial biological membrane components and their bioactivity in eukaryotic cells, encouraging similar studies in other members of the rare biosphere. [ABSTRACT FROM AUTHOR]

Nucleoside analogs are frequently used in the control of viral infections and neoplastic diseases. However, relatively few studies have shown that nucleoside analogs have antibacterial and antifungal activities. In this study, a fused pyrimidine molecule, uridine, was modified with various aliphatic chains and aromatic groups to produce new derivatives as antimicrobial agents. All newly synthesized uridine derivatives were analyzed by spectral (NMR, FTIR, mass spectrometry), elemental, and physicochemical analyses. Prediction of activity spectra for substances (PASS) and in vitro biological evaluation against bacteria and fungi indicated promising antimicrobial capability of these uridine derivatives. The tested compounds were more effective against fungal phytopathogens than bacterial strains, as determined by their in vitro antimicrobial activity. Cytotoxicity testing indicated that the compounds were less toxic. In addition, antiproliferative activity against Ehrlich ascites carcinoma (EAC) cells was investigated, and compound 6 (2′,3′-di-O-cinnamoyl-5′-O-palmitoyluridine) demonstrated promising anticancer activity. Their molecular docking against Escherichia coli (1RXF) and Salmonella typhi (3000) revealed notable binding affinities and nonbonding interactions in support of this finding. Stable conformation and binding patterns/energy were found in a stimulating 400 ns molecular dynamics (MD) simulation. Structure–activity relationship (SAR) investigation indicated that acyl chains, CH3(CH2)10CO-, (C6H5)3C-, and C2H5C6H4CO-, combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. Pharmacokinetic predictions were examined to determine their ADMET characteristics, and the results in silico were intriguing. Finally, the synthesized uridine derivatives demonstrated increased medicinal activity and high potential for future antimicrobial/anticancer agent(s). [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical Abstract

Growing location is known to affect the metabolite content and functionality of wild harvested fruits. Terminalia ferdinandiana, commonly known as Kakadu plum (KP), is among the most commercially important native Australian bush foods. Therefore, we evaluated the composition and in vitro bioactivity of aqueous acidified ethanol (AAE) and water extracts prepared from KP fruit wild harvested in the Northern Territory (NT) and Western Australia (WA). Compositional analysis included vitamin C, total ellagic acid (TEA), and total phenolic content (TPC), while in vitro bioactivity was assessed through anti-inflammatory (RAW 264.7 macrophages) activity and cell viability (Hep G2) assay. The IC50 of the extracts ranged from 33.3 to 166.3 µg/mL for NO inhibition and CC50 from 1676 to 7337 µg/mL for Hep G2 cell viability inhibition. The AAE KP fruit extracts from the NT exhibited potent anti-inflammatory activity and impacted Hep G2 cell viability more than other extracts, most likely due to TEA (3189 mg/100 g dry weight (DW)), vitamin C (180.5 mg/g DW) and TPC (196 mg GAE/g DW) being higher than in any other extract. Overall, the findings of the present study are promising for using KP fruit and derived products in functional foods, nutraceuticals, or dietary supplements.

Three biological activities were assessed for peptides obtained from two ayocote bean varieties, antioxidant and antihypertensive properties and antiproliferative activity against MDA breast cancer cells. For the peptides obtained from the ayocote bean black variety the highest antihypertensive activity was obtained with low-molecular weight peptides, principally with those between 5 and 10 kDa. However, for the peptides obtained from ayocote bean purple variety, the highest antihypertensive activity was achieved with peptides with a molecular weight ≥10 kDa, while that the higher antioxidant activity was noted for peptides obtained from ayocote bean purple variety. All peptides from both purple and black ayocote beans varieties inhibited MDA cells proliferation; however, the IC50 was only reached with high concentrations of peptides (2000 or 5000 µg*mL −1) and exposure times of 12 or 72 h. The obtained results reveal a potential relationship among the antihypertensive, antioxidant activities and anticancer properties of the peptides.

Inula viscosa is a perennial herbaceous plant native to the Mediterranean Basin, which is used topically for the treatment of various diseases in folk medicine. This study aimed to evaluate the in vivo intestinal anti-inflammatory activity of the ethanolic extract of I. viscosa (EEIV) and to test its effect on a colorectal cancer cell line. EEIV was administered to rats orally and daily at 100 and 200 mg/kg body weight for 7 days, and then colitis was induced by intrarectal instillation of 2 ml of 4% (v/v) acetic acid (AA) solution. At the end of the experiment, clinical examinations of the rats were conducted by evaluating macroscopic and histological signs of colonic tissues and measuring erythrocyte sedimentation rate (ESR) and the levels of C-reactive protein, fibrinogen, myeloperoxidase (MPO), malondialdehyde (MDA) and nitric oxide (NO). Using MTS assay, the antiproliferative effect of EEIV against human colon carcinoma HT29 cells and cytotoxicity on nondifferentiated Caco-2 cell line was evaluated. EEIV significantly decreased the ESR and fibrinogen levels as compared to control colitic rats (P < 0.001). It also significantly decreased the NO, MDA, and MPO levels in the colon tissue compared with the untreated colitic group (P < 0.001). These results were confirmed by macroscopic and histological examination, which showed significant protection against AA-induced ulcerative colitis. Furthermore, EEIV at a concentration of 369.88 μg/ml did not show cytotoxicity on confluent Caco-2 cells, with significant inhibition of colorectal cancer cell (HT29) growth (EC50 = 62.39 μg/ml). These results demonstrate that EEIV plays a potential role as a pharmacological tool in the management of inflammatory bowel disease and prevention of colorectal cancer.

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a–d against normal HEK-293 cells were in the range of 102.4–293.2 μM. Compound 5a was screened for kinase inhibitory activity, proteolytic human serum stability, and apoptotic activity. The compound was found inactive towards different kinases, while it completely degraded after 2 h of incubation with human serum. At 5 μM concentration, it induced apoptosis in MDA-MB-231 by 50.8%. Overall, these findings suggest that new benzopyran-4-one-isoxazole hybrid compounds, particularly 5a–d, are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost. Additionally, Compound 5a exhibits potential anticancer activity mediated via inhibition of cancer cell proliferation and induction of apoptosis. [ABSTRACT FROM AUTHOR]

Some new Bis-pyrazoline hybrids 8–17 with dual EGFR and BRAFV600E inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12, 15, and 17 demonstrated strong antiproliferative activity with GI50 values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAFV600E. Compounds 12, 15, and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAFV600E. Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of the antiapoptotic Bcl2. The molecular docking studies verified that compounds 12, 15, and 17 have the potential to be dual EGFR/BRAFV600E inhibitors. Additionally, in silico ADMET prediction revealed that most synthesized bis-pyrazoline hybrids have low toxicity and adverse effects. DFT studies for the two most active compounds, 12 and 15, were also carried out. The values of the HOMO and LUMO energies, as well as softness and hardness, were computationally investigated using the DFT method. These findings agreed well with those of the in vitro research and molecular docking study. [ABSTRACT FROM AUTHOR]

Cancer cells frequently develop drug resistance, which leads to chemotherapeutic treatment failure. Additionally, chemotherapies are hindered by their high toxicity. Therefore, the development of new chemotherapeutic drugs with improved clinical outcomes and low toxicity is a major priority. Several indole derivatives exhibit distinctive anti-cancer mechanisms which have been associated with various molecular targets. In this study, target compounds 4a–q were obtained through the reaction of substituted benzyl chloride with hydrazine hydrate, which produces benzyl hydrazine. Subsequently, the appropriate substituted benzyl hydrazine was allowed to react with 1H-indole-2-carboxylic acid or 5-methoxy-1H-indole-2-carboxylic acid using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a coupling agent. All compounds exhibited cytotoxicity in three cell lines, namely, MCF-7, A549, and HCT. Compound 4e exhibited the highest cytotoxicity, with an average IC50 of 2 µM. Moreover, a flow cytometry study revealed a significantly increased prevalence of Annexin-V and 7-AAD positive cell populations. Several derivatives of 4a–q showed moderate to high cytotoxicity against the tested cell lines, with compound 4e having the highest cytotoxicity, indicating that it may possess potential apoptosis-inducing capabilities. [ABSTRACT FROM AUTHOR]

Cassia fistula L. is well known for its traditional medicinal properties as an anti-inflammatory, hepatoprotective, antifungal, antibacterial, antimutagenic, and wound healing agent. The aim of the present study was to determine antioxidant, genoprotective, and cytotoxic potential of different fractions of C. fistula bark including hexane (CaMH), chloroform (CaMC), ethyl acetate (CaME), and methanol (CaMM). Among all the fractions studied, CaMM exhibited maximal radical scavenging activity in antioxidant DPPH assay, Superoxide anion radical scavenging assay and nitric oxide radical scavenging assay displayed an IC50 value of 18.95, 29.41, and 13.38 µg/ml, respectively. CaMM fraction possessed the highest phenolic (130.37 mg gallic acid equivalent/g dry weight of extract) and flavonoid (36.96 mg rutin equivalent/g dry weight of fraction) content. Data demonstrated significant positive correlation between polyphenol levels and radical scavenging activity. Single cell gel electrophoresis (Comet assay) exhibited genoprotective potential of C. fistula bark fractions against DNA damage induced by hydrogen peroxide (H2O2) in human lymphocytes. CaMM fraction displayed highest protective ability against H2O2 induced-toxicity as evidenced by significant decrease in % tail DNA content from 30 to 7% at highest concentration (200 µg/ml). CaMM was found to be rich in catechin, gallic acid, chlorogenic acid, and kaempferol. The phenolic content and antioxidant ability of the fractions was markedly negatively correlated with H2O2- induced DNA damage in human lymphocytes. Cytotoxic potential was evaluated against dermal epidermoid carcinoma (A431), pancreatic (MIA PaCa-2) and brain glioblastoma (LN-18) cancer cell lines using MTT assay. Results showed that C. fistula bark fractions possessed highest toxicity against the skin carcinoma cells. CaMM fraction reduced over 50% cell growth at the concentration of 76.72 µg/ml in A431 cells. These findings suggest that fractions of C. fistula bark exhibit potential to be considered as therapeutic agents in various carcinomas. [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]