In vitro experimental and computational study of 1,2,4-triazole derivatives as antimicrobial and anticancer agents

The 1,2,4-triazole core poses many applications in different fields, especially medicine. Based on this information, 1,2,4-triazole derivatives were studied for the antimicrobial and anticancer activities. First, the antimicrobial activity of the agents was evaluated against Gram-positive and Gram-negative bacterial strains, as well as fungal species at very low concentrations. The data revealed that 1,2,4- triazole derivatives substituted with alkyl moieties showed potency more than the aryl moieties, substituted on ortho, meta, and para positions. The agent, 4-amino-5-methyl-4H- 2-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl) acetonitrile ( 4h ), proved to have antimicrobial activity against Candida albicans at (1μg/mL). Moreover, the binding score and pose of agent ( 4h ) were inspected towards C. albicans utilizing AutoDock4.2.6 software, the docking computations results demonstrated competing binding scores for compound ( 4h ) and the co-crystallized 4C7 ligand with values of −5.5 and −5.3 kcal/mol, respectively. Secondly, for better drug delivery of the agents into the cancer cells, low density lipoprotein, polyethylene glycol, and chitosan were used to encapsulate the agents to target tubulin in liver (HEPG2) and breast (MDA-MB-453) cancer cell lines as surrogate models. The cell proliferation results demonstrated that the 1,2,4-triazole derivatives exhibited potent antiproliferative activity, effectively inhibiting cancer cell growth in both tested cell lines. All derivatives benefited from the encapsulation and drug delivery strategy and the IC 50 values were lowered after encapsulation strategy. In sum, the results confirmed that the 1,2,4-triazole derivatives displayed a potent apoptotic effect and is considered as antifungal and anticancer agent.