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Introduction: We developed and produced a new series of 4,6-diaryl-pyrimidines 9–29 as antiproliferative agents targeting EGFR/VEGFR-2. Methods: The antiproliferative efficacy of the novel targets was assessed against a panel of 60 NCI cancer cell lines and four cancer cell lines in vitro. Results and Discussion: Compounds 14 , 17 , 19 , 22 , 25 , and 29 demonstrated the greatest potency among the derivatives, with GI50 values between 22 and 33 nM; compounds 22 and 29 exhibited the highest potency, with GI50 values of 22 and 24 nM, respectively. We subsequently examined the most efficient derivatives as dual EGFR/VEGFR-2 inhibitors, finding that compounds 22 and 29 functioned as dual inhibitors. Moreover, 22 and 29 can act as apoptotic inducers by increasing Bax levels and decreasing levels of the anti-apoptotic protein Bcl2. At both 24- and 48-h intervals, the cell migration rates of compounds 22 and 29 were lower than those of untreated cells, according to the migration rate and wound closure percentage assessment. The wound closure rate reached 100% after 72 h of therapy with compound 22 but only 80% with compound 29. The docking study showed that compounds 22 and 29 had docking scores similar to those of Erlotinib and Sorafenib, co-crystallized ligands, for the EGFR and VEGFR-2 proteins. The experiments on lipophilicity showed that the new pyrimidines had a consistent result. This group of compounds has better biological activity in all the biological systems studied with low lipophilicity. [ABSTRACT FROM AUTHOR]

• Sclerocarya birrea fruit exocarp and Terminalia prunoides pods extracts have 24 poly phenolic metabolites including shikimic acid, gallic acid and quercetin-3-d-xyloside. • Sclerocarya birrea fruit exocarp, Terminalia prunoides extracts pod and their synergy inhibit the proliferation of HeLa cells. • Sclerocarya birrea fruit exocarp, Terminalia prunoides extracts pod and their synergy downregulate the expression of EGFR, VEGF, MACC1, and CYFRA 21-1 genes. • Sclerocarya birrea fruit exocarp, Terminalia prunoides extracts pod and their synergy downregulate the expression CD 95 gene. Cancer is one of the leading causes of death globally. Conventional drugs are expensive and have been reported to have side effects. This directs efforts in cancer research to search for inexpensive solutions with less or no side effects. This study aimed at screening for phytochemicals and the antiproliferative effects of Sclerocarya birrea fruit exocarp (SBFE) and Terminalia prunioides pods extracts (TPPE) on human cervical cancer cell line (HeLa). Extracts were qualitatively evaluated for their phytochemicals using HPLC and LC-MS/MS, and the antiproliferative effects by 4-[-3(4-Iodophenyl)-2-(4-nitro-phenyl)-2H-5-tetrazolio]-1,3-benzene sulfonate (WST-1) assay. HPLC and LC-MS/MS analysis led to identification and quantification of 24 polyphenolic metabolites amongst which shikimic acid (3.6014 mg g-1), gallic acid (40.8283 mg g-1), and quercetin-3-d-xyloside (3.4677 mg g-1) as the major metabolites. Results from antiproliferative effects of extracts were used to make 3 potential anticancer formulations. Furthermore, effects of extracts and formulations on the expressions of cervical cancer markers: Epidermal Growth Factor Receptor (EGFR), Metastasis-Associated in Colon Cancer 1 (MACC1), Vascular Endothelial Growth Factor (VEGF), Cytokeratin Fragment (CYFRA 21-1), and Cluster differentiation 95 (CD95) were evaluated by Reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR). Methanol and ethyl acetate extracts of both plants tested positive for saponins, tannins, flavonoids, phenols, terpenoids, cardiac glycoside and steroids. Methanol extracts were the most effective with IC 50 values of 75 µg/mL and 190 µg/mL for SBFE and TPPE respectively. The formulations: M1E1M2E2 and M1M2 had IC 50 values of 77 µg/mL and 83 µg/mL respectively. All treatments downregulated mRNA expression of EGFR, VEGF, MACC1, CYFRA 21-1, and upregulated CD 95 mRNA expression. Formulations were more effective than individual extracts against HeLa cells. However, there is need for further testing for other possible mechanisms of action and isolation of phytocompounds. [ABSTRACT FROM AUTHOR]

Breast cancer development depends critically on antiproliferative and apoptotic mechanisms. However, the mechanisms underlying the antiproliferative and apoptosis effects of breast cancer treated with tri-chalcone remain unclear. Tri-chalcones have been demonstrated in prior studies to inhibit the proliferation of breast cancer cells (MCF-7). Following the discovery, this study seeks to investigate the effect of tri-chalcone compounds on targets involved in antiproliferative and apoptosis mechanisms. In this study, we employed bioinformatics analysis along with in vitro evaluation using tri-chalcone-treated MCF-7 cells to determine the responses of antiproliferative and apoptosis mechanisms. The analysis revealed that the compounds interact with six apoptosis target receptors: TNFα, Bak, Bcl-2, caspase-9, and caspase-8. Tri-chalcone S1-2 exhibited the strongest binding affinities for TNFα (−7.39 kcal/mol), caspase-8 (−8.43 kcal/mol), caspase-9 (−8.53 kcal/mol), Bcl-2 (−8.51 kcal/mol), and Bak (−7.15 kcal/mol). The tri-chalcone S1-2 paired with the corresponding proteins showed minor flexibility and extremely small changes of less than 0.25 nm during the MD simulation. Additionally, tri-chalcone S1-2 had a significant inhibitory effect on the proliferation of MCF-7 cells (5.31 ± 0.26 µg/mL) compared to other compounds. S1-2 also induced apoptosis, affecting nearly half (43.80%) of the total early and late apoptosis in MCF-7 cells. S1-2-treated MCF-7 cells also demonstrated upregulations of genes TNFα (1.50), Bak (1.42), caspase-8 (1.24), and caspase-9 (1.61), accompanied by a downregulation of gene Bcl-2 (0.71). The discovery gives us a better understanding of how tri-chalcone S1-2 suppressed MCF-7 cell proliferation and induced apoptosis through intrinsic and extrinsic pathways. [ABSTRACT FROM AUTHOR]

Introduction:Vernonia amygdalina Delile (VAD), also known as bitter leaf, is widely utilized in traditional medicine for the treatment of various ailments, including cancer. The presence of bioactive compounds in VAD is believed to be responsible for its characteristic bitterness. In Ghana, it is a common practice to mitigate the bitterness of VAD by combining it with Citrus aurantifolia (Christm.) Swingle (lime) juice extracts, although this method lacks scientific evidence and documentation. Therefore, the antioxidant and anticancer activities of VAD and lime juice extracts (V5) and their combined effects were evaluated in vitro. Method: The antioxidant activity and cytotoxic effects of VAD extracts were determined against Jurkat, MCF‐7, HepG2, and PNT2 cells using the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay to quantify antioxidant activity and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay to assess cytotoxicity. The statistical analysis of the data was conducted using Microsoft Excel and GraphPad Prism 8.0. Linear regression was employed to determine the correlation between the concentration and the percentage of antioxidant activity, while p values were calculated using Student's t‐test. Results: The laboratory analysis focused on the extracts V1, V2, V3, V4, and V5. Briefly, V1 and V2 contained equal amounts of saponins and terpenoids. Among these, V2 exhibited the highest free radical scavenging activity, as indicated by an EC50 value of 2.14 ± 0.06 mg/mL. V2 also demonstrated cytotoxicity against the MCF‐7, HepG2, Jurkat, and PNT2 cell lines. On the other hand, V3 and V4 did not show any cytotoxic effects across all tested cell lines. In contrast, V5 was toxic to HepG2 and MCF‐7 cells but had no cytotoxic effect on Jurkat cell lines. V2 exhibited dose‐dependent cytotoxicity (0–1000 μg/mL), with the strongest inhibition observed against Jurkat cells (IC50 value = 96.341 μg/mL) and a selective index of 3.567. The difference in activity between the extracts from different parts of the plant and the extract combined with lime juice was significant (p < 0.05), indicating a synergistic effect of the phytochemicals in both VAD and lime juice. Conclusion: V2 and V5 demonstrated a remarkable antioxidant property, and they are effective in inhibiting cancer cell lines, respectively. [ABSTRACT FROM AUTHOR]

The fruit of the Mexican madroño (Arbutus arizonica) has been consumed since pre-Columbian times by North American tribes and native groups in Mexico. Despite this, reports on its chemical composition and biological activity are limited. This work aims to determine the antioxidant, antiproliferative, and digestive enzyme inhibition activities of the methanol amberlite-retained extract of Mexican madroño. Results showed that madroño fruit is rich in antioxidants: DPPH (EC50 = 0.89 ± 0.03 mg/mL), TEAC (1078 ± 4.9 μM/g), and hemolysis inhibition (IC50 = 358.07 μg/mL), with high phenolic and flavonoid content at 15.92 ± 3.2 mg GAE/g and 4.33 ± 0.3 mg CA/g, respectively. Using analytical chromatography, gallic acid, vanillic acid, chlorogenic acid, ferulic acid, quercetin, and rutin were quantified. The extract also showed α-glucosidase inhibition (IC50 = 3.1 ± 0.17 mg/mL), but no inhibition against α-amylase and lipase (>5 mg/mL), while showing antiproliferative activity against HeLa, HT-29, and MCF-7 cancer cell lines. These results point towards an interesting potential for the fruit of the A. arizonica as chemopreventive and hold potential for elaborating functional foods. [ABSTRACT FROM AUTHOR]

Introduction: The combination of BRAF and tyrosine kinase (TK) inhibitors has been demonstrated to be highly effective in inhibiting tumor development and is an approach for overcoming resistance in clinical trials. Accordingly, a novel series of 1,2,4-oxadiazole/quinazoline-4-one hybrids was developed as antiproliferative multitargeted inhibitors. Methods: The structures of the newly synthesized compounds 9a-o were validated using IR, NMR, MS, and elemental techniques. 9a-o were tested as antiproliferative agents. Results and Discussion: The results showed that the majority of the tested compounds showed significant antiproliferative action with 9b, 9c, 9h, 9k, and 9l being the most potent. Compounds 9b, 9c, 9h, 9k, and 9l were tested as EGFR and BRAF[sup V600E] inhibitors. These in vitro tests revealed that compounds 9b, 9c, and 9h are strong antiproliferative agents that may act as dual EGFR/BRAF[sup V600E] inhibitors. 9b, 9c, and 9h were further investigated for their inhibitory effect on mutant EGFR (EGFR[sup T790M]), and the results showed that the tested compounds had considerable inhibitory action. Cell cycle study and apoptosis detection demonstrated that compound 9b exhibits cell cycle arrest at the G2/M transition. Molecular docking simulations reveal the binding mechanism of the most active antiproliferative agents. [ABSTRACT FROM AUTHOR]

In our quest to develop new treatments for cancer, we synthesized and tested a series of urea‐functionalized aminothiazole‐benzazole analogs. Our primary focus was assessing their ability to inhibit the growth of breast cancer (MCF‐7) and lung adenocarcinoma (A549) cells. Using 1H NMR, 13C NMR spectra, and high resolution mass spectrometry (HRMS), we confirmed the chemical structures of these compounds. Among them, compound 8a demonstrated significant cytotoxicity against MCF‐7 cells, achieving an IC50 value of 9.6±0.6 μM. Similarly, compound 8e exhibited potent cytotoxicity against A549 cells, with an IC50 value of 9.2±1.1 μM. We further investigated the antimigration properties of all compounds that showed promising antiproliferative effects in both MCF‐7 and A549 cells. Additionally, we evaluated how these compounds impact key apoptosis‐related proteins: Caspase‐7, PARP‐1, BAX, and Bcl‐2. These proteins play crucial roles in the regulation of programmed cell death. Overall, our findings suggest that these urea‐functionalized aminothiazole‐benzazole analogs hold promise as potential anticancer agents, warranting further exploration into their mechanisms of action and therapeutic potential. [ABSTRACT FROM AUTHOR]

Several studies have proved that leguminous lectins are often explored as a potential anti-cancer agent owing to their substantial anti-cancer properties which include inhibition of cell adhesion, proliferation and colony formation. This group of carbohydrate-binding proteins is seen to cause agglutination and an increase in cancer cell cytotoxicity. The study aims to isolate and purify the lectin present in Entada rheedii, a tropical legume and analyse its significance as a potential antiproliferative agent against human colorectal cancer cells. Previously published work confirmed the lactose, galactose and cellobiose specificity of the lectin, and this lectin was isolated, purified and separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Cytotoxic assay was performed to investigate the extent of its strength as an antiproliferative protein. The purified lectin agglutinates processed chicken RBCs with a maximum hemagglutination Unit of 32. The lectin was observed to be stable when stored at 0-4°C. The antiproliferative activity of lectin from Entada rheedii was confirmed against human colorectal carcinoma cells HCT 116 with IC50 values of 188.72 μg/mL. [ABSTRACT FROM AUTHOR]

Terminalia catappa is a plant with potential for application in various antioxidant, anti-inflammatory, antimetastatic and antitumor treatments. Therefore, this study aimed to investigate anticancer properties of methanol extract derived from T. catappa leaves, using both in vitro and in silico methods. The results showed that methanol extract had inhibition of HeLa and DU145 cell lines, with respective IC50 values of 352.50 and 954.99 μg/mL. LC-MS/MS analysis identified several active compounds within the extract, including catechin, quercetin, rutin, hirsutrin, loliolide, sesquiterpene, kaempferol, apigenin, cirsiliol, cirsimaritin and demethoxycurcumin, all of which had promising anticancer potential. These compounds performed well in the in silico test. According to computational predictions, rutin (-9.1 kcal/mol), catechin (-8.0 kcal/mol) and sesquiterpene (-8.2 kcal/mol) had higher binding affinity values than cisplatin and paclitaxel (-7.5 kcal/mol). Considering these results, the compounds were potentially anticancer agents through the inhibition of the Bcl-2 protein. Finally, T. catappa active compounds can be used as alternative candidates as a chemopreventive agent. [ABSTRACT FROM AUTHOR]

Gingival carcinoma is a malignant neoplasm affecting the oral mucosa and is associated with significant morbidity and mortality. Allium ampeloprasum var. porrum water extracts have gotten a lot of attention because of their bioactive components, such as polyphenols, flavonoids, and alkaloids, which have a variety of pharmacological activities, including antiproliferative actions. This study aimed to evaluate the histological and molecular effects of Allium ampeloprasum (leek) water extract on the proliferation of the murine gingival cancer cell line. Histological evaluation was conducted to examine morphological changes induced by extract treatment. Molecular mechanisms underlying the observed histological changes were investigated using real-time polymerase chain reaction (PCR). Expression levels of key genes associated with cell proliferation and apoptosis were assessed. Histological findings revealed a dose-dependent decrease (100, 50, 25, 12.5, and 6.25 µg/ml) in cell density and altered cell shape in the treated cell line. Also, the percentage of inhibition for the oral mucosa cell line was high, with a significant P of 0.006, in the treated group compared to the control group. Additionally, water extract has an IC50 value of 61 g/ml. The P53 fold increment of gene expression is 0.6, which means the expression level in the experimental condition is 60% higher than the control. This study provides evidence for the potential antiproliferative activity of Allium ampeloprasum water extract on the oral mucosa cell line. The observed histological changes, coupled with the modulation of key genes involved in proliferation and apoptosis, suggest that leek water extract may have therapeutic implications in managing oral cancer. [ABSTRACT FROM AUTHOR]

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]

Background and Objectives: Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigating new therapeutic approaches is necessary. Materials and Methods: Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription–quantitative polymerase chain reaction technologies. Results: Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 22.13 µM (6.97 μg/mL) and 15.53 µM (4.89 μg/mL), respectively. IMBZC did not alter the cell growth of normal HEK293 cell lines. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyses revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. Conclusions: This study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC. [ABSTRACT FROM AUTHOR]

Context Virtually all parts of Salvadora persica L. (Salvadoraceae) are used in traditional medicine. The twigs and leaves are used for oral health, but leaves are far less investigated.Objective This study assesses the oral health-promoting potential of S. persica leaves with emphasis on anti-inflammatory and antiproliferative effects and provides an in depth-characterization of their metabolite profile.Materials and methods Hot-water and methanolic S. persica leaf extracts (1, 10, and 100 µg/mL) and their major constituents (5, 10, and 50 µM), were subjected to cellular assays on IL-8 and TNFα release in LPS-stimulated human neutrophils, NO-release in LPS/IFNγ stimulated mouse macrophages, and proliferation of HNO97 human tongue carcinoma cells. Metabolite profiling was performed by UHPLC-HRMS analysis. Major constituents were isolated and structurally elucidated.Results and discussion Both extracts showed pronounced anti-inflammatory activity in LPS-stimulated neutrophils. Major identified compound classes were flavonoid glycosides, the glucosinolate glucotropaeolin, phenyl- and benzylglycoside sulfates, and megastigmane glycosylsulfates, the latter ones identified for the first time in S. persica. Glucotropaeolin strongly inhibited the release of IL-8 and TNF-α (13.3 ± 2.0 and 22.7 ± 2.6% of the release of stimulated control cells at 50 µM), while some flavonoids and 3-(3′-O-sulfo-β-d-glucopyranosyloxy)-7,8-dihydro-β-ionone, a newly isolated megastigmane glycosylsulfate, were moderately active. Benzylisothiocyanate, which is likely formed from glucotropaeolin during traditional application of S. persica, showed considerable antiproliferative activity (IC50 in HNO97 cells: 10.19 ± 0.72 µM) besides strongly inhibiting IL-8 and TNFα release.Conclusions Glucotropaeolin and benzylisothiocyanate are likely implicated in the oral health-promoting effects of S. persica leaves. The chemistry and pharmacology of the newly identified megastigmane glycosylsulfates should be further evaluated.

Multidrug resistance (MDR) is considered as a major obstacle in achieving an effective treatment of breast cancer. Paclitaxel has been used to treat cancers of the cervical, breast, ovarian and brain but MDR limits its therapeutic potential. Phytochemicals have received much interest in recent decades especially in combination approaches to tackle MDR due to their negligible harm to healthy cells and synergistic potential. Considering this notion, the present study aimed at investigating the synergistic activity of 4-MTBITC and PTX against a panel of breast cancer cells. Our results revealed that the combination had a significant antiproliferative activity against T-47D cells. Mechanistic studies revealed that 4-MTBITC and PTX also promoted the production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential. In the presence of 4-MTBITC- PTX, T-47D cells were found to be arrested in the G2/M phase which also confirmed the enhancement of late apoptotic cell population in the flow cytometer analysis. In western blot experiment, the combination had a significant decrease in Bcl-xl protein level, whereas a higher level of p53, cleaved caspase-3, and cleaved caspase-9 proteins compared to individual treatment in T-47D cells. The RT-qPCR analysis also showed that the combination had significant upregulation in the gene expression of p53, cytochrome-c, Apaf-1 and downregulation in the expression of Bcl-2 gene in T-47D cells. Hence, all the results showed that a combination of 4-MTBITC-PTX significantly enhanced the apoptosis pathway in the T-47D cell line which indicates its clinical application for the treatment of breast cancer. Abbreviations: Apaf-1: Apoptotic protease activating factor 1; AO/EB: Acridine orange/ethidium bromide; Bcl-2: B-cell lymphoma 2; CI: Combination Index; Cyt-c: Cytochrome c; CO2: Carbon dioxide; DCFH-DA 2,7-Dichloroflourescein diacetate; DMEM: Dulbecco's modified Eagle's medium; ELISA: Enzyme-linked immunosorbent assay; EA: Early apoptosis; EDTA: Ethylenediaminetetraacetic acid; L929: Normal mouse fibroblast cells; LA: Late apoptosis; L: Live; 4-MTBITC: 4-methylthiobutyl isothiocyanate; MCF-7: Human breast cancer cells; MDA-MB-231: Human triple negative breast cancer cells; MMP: Mitochondria membrane potential; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide; NCCS: National Centre for Cell Science; N: Necrotic; PTX Paclitaxel; PVDF: Polyvinylidene fluoride; PAGE: Polyacrylamide gel electrophoresis; PBS: Phosphate-buffered saline; RPMI-1640: Roswell Park Memorial Institute Medium- 1640; RT-qPCR: Quantitative real-time polymerase chain reaction; ROS: Reactive oxygen species; Rh-123: Rhodamine123; g Relative centrifugal force; SDS: Sodium dodecyl sulphate; SEM: Scanning electron microscopy; T-47D: Human estrogen positive breast cancer cells; WB: Western blotting. [ABSTRACT FROM AUTHOR]

The benzoxazole is one of the most widely exploited heterocycles in drug discovery. Natural occurring and synthetic benzoxazoles show a broad range of biological activities. Many benzoxazoles are available for treating several diseases, and, to date, a few are in clinical trials. Moreover, an ever-increasing number of benzoxazole derivatives are under investigation in the early drug discovery phase and as potential hit or lead compounds. This perspective is an attempt to thoroughly review the rational design, the structure–activity relationship, and the biological activity of the most notable benzoxazoles developed during the past 5 years (period 2019–to date) in cancers, neurological disorders, and inflammation. We also briefly overviewed each target and its role in the disease. The huge amount of work examined suggests the great potential of the scaffold and the high interest of the scientific community in novel biologically active compounds containing the benzoxazole core. [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]

Abstract 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 New sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides’ cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4, 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC50 = 8.39–16.90 μM against HepG-2 and 19.57–21.15 μM against MCF-7) comparing with doxorubicin (IC50 = 13.76 ± 0.45, 17.44 ± 0.46 μM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC50 = 1.33, 0.38 μM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC50 = 0.43 μM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field.

For the first time, this study shows the nanoarchitectonic process to obtain an acetogenin-enriched nanosystem (AuNPs-Ac) using an aqueous extract from Annona cherimola Mill (ACM) composed of gold nanoparticles embedded in an organic matrix that acts as stabilizing agent and presents anti-inflammatory activity and cytotoxical effect against HepG2 cell line, promoting apoptosis. The synthesis of AuNPs-Ac was confirmed by x-ray diffraction analysis, showing metallic gold as the only phase, and the scanning transmission microscope showed an organic cap covering the AuNPs-Ac. Fourier-transformed infrared suggests that the organic cap comprises a combination of different annonaceous acetogenins, alkaloids, and phenols by the presence of bands corresponding to aromatic rings and hydroxyl groups. High-Performance Liquid Chromatography has demonstrated the presence of annonacin, a potent acetogenin, in the extract of ACM. An in vitro anti-inflammatory activity of the extract of ACM and the AuNPs-Ac was performed using the albumin denaturation method, showing a nonlinear response, which is better than sodium diclofenac salt in a wide range of concentrations that goes from 200 to 400 μ g ml−1 with both samples. The viability assay was studied using trypan blue, treating IMR90 and HepG2 at different concentrations of AuNPs-Ac. The results defined a median lethal dose of 800 μ g ml−1 against HepG2 through apoptosis according to the ratio of caspase-cleaved 9/alpha-tubulin evaluated. It was also demonstrated that the nanosystem presents a higher cytotoxic effect on the HepG2 cell line than in IMR90, suggesting a targeted mechanism. In addition, the nanosystem performs better than using only the extract of ACM in the anti-inflammatory or antiproliferative test, attributed to their higher surface area. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells, and it is the most frequent form of leukemia diagnosed in Western countries. It is characterized by the proliferation and accumulation of neoplastic B lymphocytes in the blood, lymph nodes, bone marrow and spleen. We report the synthesis and antiproliferative effects of a series of novel ethanoanthracene compounds in CLL cell lines. Structural modifications were achieved via the Diels–Alder reaction of 9-(2-nitrovinyl)anthracene and 3-(anthracen-9-yl)-1-arylprop-2-en-1-ones (anthracene chalcones) with dienophiles, including maleic anhydride and N-substituted maleimides, to afford a series of 9-(E)-(2-nitrovinyl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones, 9-(E)-3-oxo-3-phenylprop-1-en-1-yl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones and related compounds. Single-crystal X-ray analysis confirmed the structures of the novel ethanoanthracenes 23f, 23h, 24a, 24g, 25f and 27. The products were evaluated in HG-3 and PGA-1 CLL cell lines (representative of poor and good patient prognosis, respectively). The most potent compounds were identified as 20a, 20f, 23a and 25n with IC50 values in the ranges of 0.17–2.69 µM (HG-3) and 0.35–1.97 µM (PGA-1). The pro-apoptotic effects of the potent compounds 20a, 20f, 23a and 25n were demonstrated in CLL cell lines HG-3 (82–95%) and PGA-1 (87–97%) at 10 µM, with low toxicity (12–16%) observed in healthy-donor peripheral blood mononuclear cells (PBMCs) at concentrations representative of the compounds IC50 values for both the HG-3 and PGA-1 CLL cell lines. The antiproliferative effect of the selected compounds, 20a, 20f, 23a and 25n, was mediated through ROS flux with a marked increase in cell viability upon pretreatment with the antioxidant NAC. 25n also demonstrated sub-micromolar activity in the NCI 60 cancer cell line panel, with a mean GI50 value of 0.245 µM. This ethanoanthracene series of compounds offers potential for the further development of lead structures as novel chemotherapeutics to target CLL. [ABSTRACT FROM AUTHOR]

This study focuses on the synthesis of azo‐thiosemicarbazone ligand, which is designed by reacting 2‐hydroxy‐5‐(phenyldiazenyl)benzaldehyde with hydrazine carbothioamide. Hence, this ligand was exploited for chelation with nickel and cupric salts in (1 M:1 L) molar ratio. These synthetics were structurally investigated using a variety of physical, analytical, and spectroscopic (1D/2D‐NMR, UV–Vis, FT‐IR, and E‐mass) tools as well as theoretically. The finding demonstrated that the resulting azo‐thiosemicarbazone (H4Azo‐TSC) bonded with the nickel and cupric ions as mono/di‐basic tridentate chelators, binding them via deprotonated phenolic oxygen, imino nitrogen, and thionic/thiol sulfur atoms adopting square planar geometry. The theoretical investigation was examined by DFT/B3LYP/LanL2dZ, including energetic parameters, HOMO‐LUMO energy gap, dipole moment, and geometrical optimization, which were applied to support the complexes' geometrical structure. The in vitro microbicidal activities of the azo‐thiosemicarbazone, compared with its Ni2+ and Cu2+ complexes, display superior activity over the metal complexes against different bacterial and fungal species. The anticancer efficacy of the synthetics was tested against human lung fibroblast (WI38) and mammary gland breast cancer (MCF‐7) compared with Doxorubicin as a standard drug. The cytotoxic efficiency of metallic complexes exceeded that of un‐chelated azo‐thiosemicarbazone. The most effective complex is Ni2+ complex with IC50 equal to 11.75 and 14.05 μg/ml, respectively. It has been demonstrated that Ni2+ and Cu2+ complexes are more biocompatible than free azo‐thiosemicarbazone; this finding may be related to the chelation process. [ABSTRACT FROM AUTHOR]

Medicinal plants offer natural cures and inspire modern medicine's development. This study examined the antioxidant, enzyme-inhibitory, and antiproliferative activities of various extracts obtained from aerial and root fragments of Phlomoides molucelloides (Bunge) Salmaki. The extracts' overall phenolics, flavonoids, and compounds were defined using colorimetric and LC-MS/MS analyses. The highest total phenolic and flavonoid content was measured in the methanol and infusion extracts of the aerial fragments, with 102.21 mg RE/g and 51.33 mg GAE/g, respectively. Most compounds were defined as flavonoids, predominantly as apigenin and quercetin glycosides. Methanol, 70 % methanol, and infusion extracts from aerial parts had the highest antioxidant activity determined by DPPH, ABTS, CUPRAC, FRAP, metal chelation, and phosphomolybdenum analyses. Moreover, the methanol extract of the roots had the highest anti-acetylcholinesterase, anti-butyrylcholinesterase, and anti-glucosidase activities. The dichloromethane extracts of the roots displayed the highest anti-tyrosinase and anti-amylase activities. The antiproliferative activity of the extracts was investigated against MDA-MB-231, MCF-7, and HeLa cell lines. The lowest IC 50 value (875.7 µg/mL) was computed for the methanol extract of the aerial part on the MCF-7 cell line at the 48th h. The findings showed that P. molucelloides extracts may offer a promising therapeutic approach due to their rich bioactive content. [Display omitted] • Antioxidant and enzyme-inhibitory properties of the extracts were carried out. • The extracts' phenolic and flavonoid content and compounds were defined. • The anticancer activity of the extracts was studied by MTT assay. • P. molucelloides extracts may offer a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

The article presents a study which explored the antioxidant and antiproliferative properties of Arbutus (A.) andrachne and identified the phytochemicals in A. andrachne essential oil. Topics discussed include chemicals and laboratory equipment employed by the study from reputable suppliers, preparation of crude extracts from fruits of Arbutus andrachne, and in vitro antioxidant potential of Arbutus andrachne fruits crude extracts.

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]

Cancer is a global health problem, with the incidence rate estimated to reach 40% of the population by 2030. Although there are currently several therapeutic methods, none of them guarantee complete healing. Plant-derived natural products show high therapeutic potential in the management of various types of cancer, with some of them already being used in current practice. Among different classes of phytocompounds, pentacyclic triterpenoids have been in the spotlight of research on this topic. Ursolic acid (UA) and its structural isomer, oleanolic acid (OA), represent compounds intensively studied and tested in vitro and in vivo for their anticancer and chemopreventive properties. Since natural compounds can rarely be used in practice as such due to their characteristic physico-chemical properties, to tackle this problem, their derivatization has been attempted, obtaining compounds with improved solubility, absorption, stability, effectiveness, and reduced toxicity. This review presents various UA and OA derivatives that have been synthesized and evaluated in recent studies for their anticancer potential. It can be observed that the most frequent structural transformations were carried out at the C-3, C-28, or both positions simultaneously. It has been demonstrated that conjugation with heterocycles or cinnamic acid, derivatization as hydrazide, or transforming OH groups into esters or amides increases anticancer efficacy. [ABSTRACT FROM AUTHOR]

Pyridine, a compound with a heterocyclic structure, is a key player in medicinal chemistry and drug design. It is widely used as a framework for the design of biologically active molecules and is the second most common heterocycle in FDA-approved drugs. Pyridine is known for its diverse biological activity, including antituberculosis, antitumor, anticoagulant, antiviral, antimalarial, antileishmania, anti-inflammatory, anti-Alzheimer's, antitrypanosomal, antimalarial, vasodilatory, antioxidant, antimicrobial, and antiproliferative effects. This review, spanning from 2022 to 2012, involved the meticulous identification of pyridine derivatives with antiproliferative activity, as indicated by their minimum inhibitory concentration values (IC50) against various cancerous cell lines. The aim was to determine the most favorable structural characteristics for their antiproliferative activity. Using computer programs, we constructed and calculated the molecular descriptors and analyzed the electrostatic potential maps of the selected pyridine derivatives. The study found that the presence and positions of the -OMe, -OH, -C=O, and NH2 groups in the pyridine derivatives enhanced their antiproliferative activity over the cancerous cellular lines studied. Conversely, pyridine derivatives with halogen atoms or bulky groups in their structures exhibited lower antiproliferative activity. [ABSTRACT FROM AUTHOR]

Ovarian cancer ranks among the most severe forms of cancer affecting the female reproductive organs, posing a significant clinical challenge primarily due to the development of resistance to conventional therapies. This study investigated the effects of the chalcone derivative 1C on sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines. Our findings revealed that 1C suppressed cell viability, induced cell cycle arrest at the G2/M phase, and triggered apoptosis in both cell lines. These effects are closely associated with generating reactive oxygen species (ROS). Mechanistically, 1C induced DNA damage, modulated the activity of p21, PCNA, and phosphorylation of Rb and Bad proteins, as well as cleaved PARP. Moreover, it modulated Akt, Erk1/2, and NF-κB signaling pathways. Interestingly, we observed differential effects of 1C on Nrf2 levels between sensitive and resistant cells. While 1C increased Nrf2 levels in sensitive cells after 12 h and decreased them after 48 h, the opposite effect was observed in resistant cells. Notably, most of these effects were suppressed by the potent antioxidant N-acetylcysteine (NAC), underscoring the crucial role of ROS in 1C-induced antiproliferative activity. Moreover, we suggest that modulation of Nrf2 levels can, at least partially, contribute to the antiproliferative effect of chalcone 1C. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer is one of the leading causes of death among women globally due to the limitation of current treatment methods and their associated adverse side effects. Launaea cornuta is used as traditional medicine for the treatment of a variety of diseases including cancer. However, there is no scientific validation on the antiproliferative activity of L. cornuta against cervical cancer. Objective: This study aimed to evaluate the selective antiproliferative, cytotoxic and antimigratory effects of L. cornuta and to explore its therapeutical mechanisms in human cervical cancer cell lines (HeLa-229) through a network analysis approach. Materials and methods: The cytotoxic effect of L. cornuta ethyl acetate fraction on the proliferation of cervical cancer cells was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) bioassay and the antimigratory effect was assessed by wound healing assays. Compounds were analysed using the qualitative colour method and gas chromatographymass spectroscopy (GC-MS). Subsequently, bioinformatic analyses, including the protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis, were performed to screen for potential anticervical cancer therapeutic target genes of L. cornuta. Molecular docking (MD) was performed to predict and understand the molecular interactions of the ligands against cervical cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to validate the network analysis results. Results: L. cornuta ethyl acetate fraction exhibited a remarkable cytotoxic effect on HeLa-229 proliferation (IC50 of 20.56 ± 2.83 µg/mL) with a selectivity index (SI) of 2.36 with minimal cytotoxicity on non-cancerous cells (Vero-CCL 81 (IC50 of 48.83 ± 23.02). The preliminary screening revealed the presence of glycosides, phenols, saponins, terpenoids, quinones, and tannins. Thirteen compounds were also identified by GC-MS analysis. 124 potential target genes associated with the effect of L. cornuta ethyl acetate fraction on human cervical cancer were obtained, including AKT1, MDM2, CDK2, MCL1 and MTOR were identified among the top hub genes and PI3K/Akt1, Ras/MAPK, FoxO and EGFR signalling pathways were identified as the significantly enriched pathways. Molecular docking results showed that stigmasteryl methyl ether had a good binding affinity against CDK2, ATK1, BCL2, MDM2, and Casp9, with binding energy ranging from -7.0 to -12.6 kcal/mol. Tremulone showed a good binding affinity against TP53 and P21 with -7.0 and -8.0 kcal/mol, respectively. This suggests a stable molecular interaction of the ethyl acetate fraction of L. cornuta compounds with the selected target genes for cervical cancer. Furthermore, RT-qPCR analysis revealed that CDK2, MDM2 and BCL2 were downregulated, and Casp9 and P21 were upregulated in HeLa-229 cells treated with L. cornuta compared to the negative control (DMSO 0.2%). Conclusion: The findings indicate that L. cornuta ethyl acetate fraction phytochemicals modulates various molecular targets and pathways to exhibit selective antiproliferative and cytotoxic effects against HeLa-229 cells. This study lays a foundation for further research to develop innovative clinical anticervical cancer agents. [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]

Objectives: This study investigates the in vitro efficient pathway for the callus induction from nodal explant and isolation of the Shatavarin-IV from the callus extract from fresh callus and Dry callus. The effect of Shatavarin IV was examined on the Human lung carcinoma cell line. Gene expression study was carried out using a specific primer to conform weather it is anticancer compound or not. Materials and Methods: In the present study, 2,4-D and Kn were used for the direct callus induction. Callus culture, organogenesis and cell culture are used to harvest secondary metabolites. Quantification of Shatavarin-IV was performed using a TLC scanner at a wavelength of 425 nm. HPTLC analysis was performed to quantitatively determine the presence of Shatavarin-IV in Fresh Callus (FC), Dry Callus (DC) and Root Extract (RE). The mobile phase used for HPTLC analysis was ethyl acetate: methanol: water: formic acid (7.5:1.5:1:0.2 v/v). Extraction was carried out using 80% methanol and the extract was filtered. The extract was then analyzed using HPTLC methods. Further, the effect of Shatavarin-IV was studied on the human lung carcinoma cell line NCI-H23. The end result of cell cytotoxicity was analyzed using MTT dye. To, confirm whether the cell expressed an apoptotic gene or not RTPCR studies were been carried out. Results: The best hormonal combination for callus induction from nodal explant was found 11.31 µM 2,4-D combined with 4.64 µM Kn on MS as basal media. Shatavarin-IV accumulation in dry callus was 0.0305% w/w, wild-grown plant root extract showed 0.01732% w/w and in fresh callus presence of Shatavarin-IV was 0.0012% w/w. IC50 of the Shatavarin-IV was 0.8 Micromolar dissolved in DMSO. Gene expression study reflects the multifold increase of the BAX and decrease of BCL2, concluded interpreted as Shatavarin-IV causes apoptotic gene expression. Conclusion: It was concluded that, Shatavarin IV reduced the expression of BCL2 and increase BAX expression which positive sign that Shatavarin IV act as an anticancer compound. Shatavarin IV can be isolated from the in vitro callus culture, which can be alternative of whole plant that was exploited for its medicinal properties. (Schematic Abstract). [ABSTRACT FROM AUTHOR]

The chemical composition of extracts (CEs) and essential oils (EOs) from Tetradenia riparia leaves, flower buds, and stems was analyzed. Antiproliferative activity against tumor cell lines, NO production inhibition, and antioxidant and antiviral activities were assessed. The CEs contained flavonoids, phenolic acids, coumarins, and saturated fatty acids. The EOs included monoterpenes, oxygenated sesquiterpenes, and diterpenes. NO production inhibition ranged from 76 to 247 µg mL−1, and antiproliferative activity exhibited GI50 between 20 and >204 µg mL−1, with low cytotoxicity (SI: 1.08 to 4.75). Reactive oxygen species inhibition ranged from 45 to 82%. Antioxidant activity varied when determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (IC50: 0.51 to 8.47 mg mL−1) and ferric reducing antioxidant power (0.35 to 0.81 µM ferrous sulfate per mg). The reduction in β-carotene–linoleic acid co-oxidation varied between 76.13 and 102.25%. The total phenolic content of CEs and EOs was 10.70 to 111.68 µg gallic acid mg−1. Antiviral activity against herpes simplex virus type 1 (HSV-1) showed an EC50 between 9.64 and 24.55 µg mL−1 and an SI between 8.67 and 15.04. Leaf EOs exhibited an EC50 of 9.64 µg mL−1 and an SI of 15.04. Our study unveils the diverse chemical composition and multifaceted pharmacological properties of T. riparia, demonstrating its potential as a valuable source of bioactive compounds for therapeutic applications. [ABSTRACT FROM AUTHOR]

The study aimed to comprehensively identify the phenolic fingerprint of Morina persica L. (Caprifoliaceae) and evaluate its various biological activities. LC-MS/MS analysis of 70% Morina persica methanol extract revealed the presence of 27 phytochemicals, with quinic acid, chlorogenic acid, and rutin being the major phenolics. The antioxidant, antibacterial, antiproliferative, and cytotoxic activities were evaluated for biological screening. The results showed that the methanolic extract of M. persica has a moderate DPPH radical scavenging and ferric-reducing capacity, indicating antioxidant activity. M. persica was observed to have a sufficient antiproliferative effect against cancer cells and low cytotoxicity against normal cells. Moreover, M. persica demonstrated good antibacterial activity against Clostridium perfringens, Enterococcus faecalis, and Escherichia coli. These data suggest that the methanolic extract of M. persica could be considered both an industrial source of quinic acid and a potential biologically active ingredient for developing drug formulations. [ABSTRACT FROM AUTHOR]

Asystasia gangetica leaves were extracted sequentially with different solvent systems. The quantitative estimation of secondary metabolites along with antioxidant activities were evaluated. Methanol extract had the highest phenolics (12.82 mg of GAE g−1 DW), condensed tannins (13.81 mg of GAE g−1 DW), saponin (10.71 mg of DE g−1 DW) content along with highest DPPH radical (IC50 of 62.40 μg mL−1), ABTS radical (22.70 μg mL−1) scavenging activity, and CUPRAC (65.86 TE g−1 DW) total antioxidant activity. The mild antimitotic and antiproliferative effects of extracts suggest low toxicity. The extracts demonstrated potential in vitro anti-inflammatory activity. Polyphenols, including novel Isovitexin, Genestin, Syringic acid, and Caffeic acid were the major metabolites identified. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, Silver Nanoparticles (AgNPs) have demonstrated a wide range of antioxidant and anticancer properties. Vinca alkaloid exhibits the anticancer efficacy by direct metaphase arrest of cell division. Aim: The present study is to develop a green synthesis method for producing silver nanoparticles using vinca, the antioxidant and anticancer potential was assessed using A549 cells. Materials and Methods: The synthesized AgNPs were analyzed using Fourier Transform Infrared (FTIR) analysis, UV-visible spectrophotometer (UV), Scanning Electron Microscope (SEM) and Spectra Max i3X energy-dispersive X-ray (XRD) Spectroscopy to determine their physico-chemical and morphological characteristics. Results and Discussion: The FTIR spectrum of vinca AgNPs exhibited absorption bands at 692 cm-1, 684 cm-1, 611 cm-1, 592 cm-1, 578 cm-1, 554 cm-1, 548 cm-1, 539 cm-1 and 526 cm-1, indicating the presence of silver ion bounded nanoparticles derived from Vinca leaf. These findings suggest that vinca-coated AgNPs possess multiple functions that contribute to their stability. XRD data analysis revealed Bragg's reflections in the XRD pattern (2θ) at 24.75, 31.59, 37.56, 53.01, 64.93 and 76.27, confirming the crystalline nature of the green synthesized AgNPs. Elemental analysis was conducted to determine the elemental composition of the sample, which indicated that approximately 60% of the prepared nanoparticles were bound with silver ions, supporting the formulation. Antioxidant studies were performed using the DPPH assay at different concentrations of AgNPs, while cell-based cytotoxic assays were conducted using different concentrations of AgNO3. Conclusion: The results demonstrated that the nanoparticles inhibited the proliferation of A549 cells and reduced cellular motility, indicating their promising anticancer efficacy. [ABSTRACT FROM AUTHOR]

The species of the genus Euphrasia present important medicinal potential according to their traditional uses. However, few studies aim to sustain this fact by scientific evidence. The present study aimed to explore the phytochemical profile and investigate the antioxidant, antimicrobial and antiproliferative potential of E. officinalis subsp. pratensis Fr. (EO) and E. stricta J.P.Wolff ex J.F.Lehm (ES). The tested samples consisted of ethanolic extracts. The identification and quantification of phenolic compounds were performed using spectrophotometric and LC–MS/MS methods. The antioxidant capacity was evaluated using the DPPH, FRAP and xanthine oxidase methods. Antimicrobial properties were screened using disk diffusion, broth microdilution and anti-biofilm assays, while antiproliferative potential was assessed on a colorectal adenocarcinoma human cancer cell line (DLD-1). The LC–MS/MS analysis showed chlorogenic acid and rutin as the dominant constituents in the tested extracts. The antioxidant activity assays showed important capacity for both samples; in vitro antimicrobial and anti-biofilm properties were exhibited, especially against Gram-positive bacteria, and an important inhibitory potential was observed on the proliferation of the DLD-1 cell line. The findings in the present study contribute to the recommendation of EO and ES for the prevention and treatment of oxidative stress-related pathologies, cancer and microbial infections. [ABSTRACT FROM AUTHOR]

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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]

Introduction: Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to cigarette smoke can be modified, making it difficult to eliminate opportunistic microorganisms. The leaves of Eugenia pyriformis are a by-product of fruit production and, to date, there have been no studies addressing the antiproliferative, anti-inflammatory, and antimicrobial activities. Objective: Investigate the antimicrobial, Nitric Oxide (NO)-production inhibition, and antiproliferative activities of the essential oil from E. pyriformis leaves and its possible effect on the treatment and prevention of damage caused by tobacco. Methods: The essential oil (EO) was obtained by hydrodistillation (3 h). Its chemical composition was investigated by GC-MS. It was proposed to investigate antiproliferative activity against human tumor cell lines, namely, breast adenocarcinoma (MCF-7), lung (NCI-H460), cervical (HeLa), and hepatocellular (HepG2) carcinomas. A non-tumor primary culture from pig liver (PLP2) was also tested. The EO capacity to inhibit nitric oxide (NO) production was evaluated by a lipopolysaccharide stimulated murine macrophage cell line. Antibacterial and antifungal activities against opportunistic pathogens were investigated against seven strains of bacteria and eight fungi. Results: The results indicated the presence of 23 compounds in the essential oil, the majority were spathulenol (45.63%) and β-caryophyllene oxide (12.72%). Leaf EO provided 50% inhibition of nitric oxide production at a concentration of 92.04 µg mL−1. The EO also demonstrated antiproliferative activity against all human tumor cell lines studied, with GI50 values comprised between 270.86 and 337.25 µg mL−1. The essential oil showed antimicrobial potential against the bacteria Listeria monocytogenes (Murray et al.) Pirie (NCTC 7973) and Salmonella Typhimurium ATCC 13311 (MIC 1870 µg mL−1) and fungi Aspergillus versicolor ATCC 11730, Aspergillus ochraceus ATCC 12066, Penicillium ochrochloron ATCC 90288, Penicillium verrucosum var. cyclopium (Westling) Samson, Stolk & Hadlok (food isolate) (MIC 1870 µg mL−1) and Trichoderma viride Pers. IAM 5061 (1,400 µg mL–1).Conclusion: The demonstrated anti-inflammatory, antiproliferative, and antimicrobial activities in the leaves of E. pyriformis can add value to the production chain of this plant, being a possible option for preventing and combating cancer, including lung cancer. [ABSTRACT FROM AUTHOR]

Olea europaea (OFE) and Ficus carica (FFE) extracts have shown anticancer activity. In the currents report, we aim to evaluate the phytochemical composition, antioxidant properties and anticancer activity of OFE and FFE against PANC-1 and AsPC-1 pancreatic cancer cell lines. OFE possessed higher phenolic, flavonoid content and antioxidant ability than FFE. OFE and FFE induced a cytotoxic effect and their combination resulted in an increased cytotoxicity. OFE showed an antiproliferative effect while FFE had no effect. Combination of the two extracts resulted in an antiproliferative effect similar to that of OFE. OFE showed an anti-migratory effect, while FFE exhibited a promigratory effect. Interestingly, combination of the two extracts resulted in an anti-migratory effect similar to that caused by OFE. In view of the findings of this study, these extracts could be considered potential sources of natural compounds with antioxidant and anti-pancreatic cancer effects. The combination of these extracts should be further investigated in the context of pancreatic cancer. [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]

Objective: Research has demonstrated that Leptospermum scoparium possesses various therapeutic benefits. This study set out to determine whether or not L. scoparium extracts had any effect on the ability of HepG2 and MCF-7 breast cancer cells to survive. Materials and Methods: The antiproliferative activity of L. scoparium extracts was explored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. The most active fraction was selected to investigate its effects on apoptosis induction using flow cytometry and quantitative real-time polymerase chain reaction. The constituents of this fraction were characterized using GC-MS analysis. Results: Research demonstrated that the chloroform fraction of L. scoparium (LSCF) significantly impacted the HepG2 and MCF-7 cancer cell lines. Treatment with LSCF led to a notable rise in both early and late apoptotic cells. Furthermore, there was an upregulation in the mRNA levels of P53, Bax, and caspases, while the expression of Bcl-2 mRNA saw a decrease. The analysis of LSCF revealed the primary components to be cis-calamenene, beta-eudesmol, cyclododecane, and alpha-muurolene. Conclusion: The study showed the promising antiproliferative activity of L. scoparium, suggesting its potential application for cancer treatment. [ABSTRACT FROM AUTHOR]

IntroductionWe developed and produced a new series of 4,6-diaryl-pyrimidines 9–29 as antiproliferative agents targeting EGFR/VEGFR-2.MethodsThe antiproliferative efficacy of the novel targets was assessed against a panel of 60 NCI cancer cell lines and four cancer cell lines in vitro.Results and DiscussionCompounds 14, 17, 19, 22, 25, and 29 demonstrated the greatest potency among the derivatives, with GI50 values between 22 and 33 nM; compounds 22 and 29 exhibited the highest potency, with GI50 values of 22 and 24 nM, respectively. We subsequently examined the most efficient derivatives as dual EGFR/VEGFR-2 inhibitors, finding that compounds 22 and 29 functioned as dual inhibitors. Moreover, 22 and 29 can act as apoptotic inducers by increasing Bax levels and decreasing levels of the anti-apoptotic protein Bcl2. At both 24- and 48-h intervals, the cell migration rates of compounds 22 and 29 were lower than those of untreated cells, according to the migration rate and wound closure percentage assessment. The wound closure rate reached 100% after 72 h of therapy with compound 22 but only 80% with compound 29. The docking study showed that compounds 22 and 29 had docking scores similar to those of Erlotinib and Sorafenib, co-crystallized ligands, for the EGFR and VEGFR-2 proteins. The experiments on lipophilicity showed that the new pyrimidines had a consistent result. This group of compounds has better biological activity in all the biological systems studied with low lipophilicity.