Nada M. Ali

The dual global health crises of antimicrobial resistance and cancer demand the urgent discovery of novel therapeutic leads. The medicinal plants Cynanchum viminale and Pergularia daemia (Apocynaceae) represent a rich reservoir of bioactive compounds used in traditional medicine, yet a comprehensive comparative analysis of their bioactivities and molecular mechanisms has remained elusive. This study provides an integrated in vitro and in silico analysis of the methanolic extracts of C. viminale and P. daemia. Phytochemical profiles were delineated by HPLC. Bioactivities were systematically evaluated via a battery of five antioxidant assays (DPPH, ABTS, FRAP, H₂O₂, NO), broad-spectrum antimicrobial screening against six pathogens, and cytotoxicity assays against a panel of six human cancer cell lines (HepG-2, MCF-7, HCT-116, A-549, PC-3, A-431). To deconstruct the molecular basis of these activities, in silico molecular docking was performed against two pivotal therapeutic targets: Epidermal Growth Factor Receptor (EGFR) and Dihydrofolate Reductase (DHFR). A striking functional divergence between the two plants was discovered. P. daemia exhibited superior antioxidant and broader-spectrum antibacterial activity, a finding strongly correlated with its unique phenolic profile, particularly the potent DHFR-binding Chlorogenic acid and the bioenhancing alkaloid Piperine. In stark contrast, C. viminale demonstrated dramatically superior cytotoxic potency across all tested cancer cell lines, with IC₅₀ values as low as 24.37 µg/mL against HepG-2 liver cancer. Molecular docking brilliantly illuminated the mechanism behind this divergence: the potent cytotoxicity of C. viminale is driven by its principal alkaloids, Protopine and Berberine, which showed high-affinity binding to the ATP-binding site of EGFR, a key driver of cancer proliferation. DHFR, conversely, was identified as a common molecular target for potent binders from both plants (Evodiamine, Piperine, Chlorogenic acid), providing a unifying mechanism for their shared antimicrobial properties.

Cancer and microbial infections constitute a major burden and leading cause of death globally. The development of therapeutic compounds from natural products is considered a cornerstone in drug discovery. Therefore, in the present study, the ethanolic extract and the fractions of Dodonaea viscosa and Juniperus procera were evaluated for anticancer and antimicrobial activities. It was found that two fractions, JM and DC, exhibited promising anticancer and antimicrobial activities. The JM and DC fractions were further modified into ZnO nanocomposites, which were characterized by SEM, XRD, TGA, and EDX. It was noted that the synthesized nanocomposites displayed remarkable enhancement in cytotoxicity as well as antibacterial activity. Nanocomposite DC–ZnO NRs exhibited cytotoxicity with IC₅₀ values of 16.4 ± 4 (HepG2) and 29.07 ± 2.7 μg/mL (HCT-116) and JM–ZnO NRs with IC₅₀ values of 12.2 ± 10.27 (HepG2) and 24.1 ± 3.0 μg/mL (HCT-116). In addition, nanocomposites of DC (i.e., DC–ZnO NRs) and JM (i.e., JM–ZnO NRs) displayed excellent antimicrobial activity against Staphylococcus aureus with MICs of 2.5 and 1.25 μg/mL, respectively. Moreover, these fractions and nanocomposites were tested for cytotoxicity against normal fibroblasts and were found to be non-toxic. GC-MS analysis of the active fractions were also carried out to discover the possible phytochemicals that are responsible for these activities.

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC₅₀ 1.1 μM), HCT-116 (IC₅₀ 2.6 μM), and HepG2 (IC₅₀ 1.4 μM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC₅₀ in the range 1.95–4.24 μM, whereas the standard drug, Pemetrexed, showed IC₅₀ 7.26 μM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential.

Many medicinal plants have been used to treat and prevent illnesses in Saudi Arabia. The present study aimed to investigate the chemical composition of Mentha viridis obtained from Albaha region of Saudi Arabia and evaluate its antimicrobial and antiproliferative potential. The extract was obtained from plant fresh material and identified by gas chromatography-mass spectrometry (GC-MS). The antimicrobial and antiproliferative potential of the plant extract was analysed by performing four subsequent extracts: ethanol, petroleum ether, chloroform, and methanol. The GC-MS analysis showed carvone as a main component, as it comprised 64.82% of the plant extract. In antimicrobial activity, methanol extract showed significant activity against Pseudomonas aeruginosa with zone of inhibition of 15 mm. The MTT assay showed that petroleum ether and chloroform extracts have moderate cytotoxic effect against MCF-7 breast cancer cell line with IC50 values of 193.23 mu g/mL and 131.86 mu g/mL, respectively. Chloroform extract also showed mild activity against HCT-116 colorectal cancer cell line with IC50 value of 189.2 mu g/mL. This study highlights the potential of M. viridis extracts as powerful bioactive phytochemicals with possible role in diseases and cancer therapy.

Thymidylate synthase (TS) has emerged as a hot spot in cancer treatment, as it is directly involved in DNA synthesis. In the present article, nine hybrids containing 1,2,3-triazole and 1,3,4-oxadiazole moieties (6–14) were synthesized and evaluated for anticancer and in vitro thymidylate synthase activities. According to in silico pharmacokinetic studies, the synthesized hybrids exhibited good drug likeness properties and bioavailability. The cytotoxicity results indicated that compounds 12 and 13 exhibited remarkable inhibition on the tested Michigan Cancer Foundation (MCF-7) and Human colorectal Carcinoma (HCT-116) cell lines. Compound 12 showed four-fold inhibition to a standard drug, 5-fluoruracil, and comparable inhibition to tamoxifen, whereas compound 13 exerted five-fold activity of tamoxifen and 24-fold activity of 5-fluorouracil for MCF-7 cells. Compounds 12 and 13 inhibited thymidylate synthase enzyme, with an half maximal inhibitory concentration, IC₅₀ of 2.52 µM and 4.38 µM, while a standard drug, pemetrexed, showed IC₅₀ = 6.75 µM. The molecular docking data of compounds 12 and 13 were found to be in support of biological activities data. In conclusion, hybrids (12 and 13) may inhibit thymidylate synthase enzyme, which could play a significant role as a chemotherapeutic agent.