Molecular docking studies, biological evaluation and synthesis of novel 3-mercapto-1,2,4-triazole derivatives

Synthesis of bioactive heterocyclic compounds having effective biological activity is an essential research area for wide-ranging applications. In this study, a conventional methodology has been developed for the synthesis of a series of new 3-mercapto-1,2,4-triazole derivatives 4a-f. The purity and structure of the synthesized molecules were confirmed by ¹H NMR, ¹³C NMR and elemental analysis. In addition, the prepared compounds were screened for their anti-proliferative activity against three human cancer cell lines including A549 (lung cancer), MCF7 (breast cancer) and SKOV3 (ovarian cancer) using MTT reduction assay. All the tested compounds demonstrated remarkable cytotoxic activity with IC₅₀ values ranging from 3.02 to 15.37 µM. The heterocyclic compound bearing 3,4,5-trimethoxy moiety was found to be the most effective among the series displaying an IC₅₀ of 3.02 µM specifically against the ovarian carcinoma cancer cell line (SKOV3). Moreover, Annexin V-FITC/propidium iodide staining assay indicated that this compound can induce apoptosis in SKOV3 cells. Furthermore, cell cycle assay showed a significant cell cycle arrest at the G2/M phase in a dose-dependent manner for this compound. The molecular docking results was showed binding modes of potent compound 4d perfectly corroborated the suggestion of binding to the colchicine site. The entire results conclude that 3-mercapto-1,2,4-triazole derivatives can be synthesized by a green method for biological and pharmacological applications. New analogs of 3-mercapto-1,2,4-triazole potential derivatives for anti-proliferative activity were synthesized. Cytotoxic activity of all synthesized compounds was evaluated against tree human cancer cell lines: lung (A549), breast (MCF7) and ovarian (SKOV3).