Design, synthesis, and computational studies of pyridine-substituted 1,2,3-triazoles with anticancer and antibacterial activities

A new series of pyridine-based 1,2,3-triazole derivatives (SD5–7) was synthesized through Cu(I)-catalyzed azide–alkyne cycloaddition and fully characterized by FT-IR, NMR, HRMS, and elemental analysis. The molecular structures of SD6 and SD7 were further confirmed by single-crystal X-ray diffraction, which revealed stabilizing π–π stacking and weak intermolecular interactions. Additionally, the properties of compounds SD5, SD6, and SD7 were investigated by density functional theory using B3LYP/6-311G*. Cytotoxic properties were investigated against OUMS (cancerous) and HUVEC (healthy) cell lines using MTS assays. SD5 exhibited the most potent effect on OUMS cells (IC50 = 98.05 µg/mL), exceeding the activity of cisplatin, while SD6 displayed statistically significant selectivity between cancer and normal cells. Antibacterial screening against Gram-positive (S. aureus, B. cereus) and Gram-negative (E. coli, K. pneumoniae) strains showed that SD5 and SD6 had moderate inhibitory effects (MIC = 5 mg/mL), whereas SD7 was inactive. These results suggest that pyridine-substituted 1,2,3-triazoles represent valuable scaffolds with promising dual anticancer and antibacterial potential for further development. Compounds SD5–7 exhibited cytotoxic effects against the OUMS cell line within the concentration range of 98.05–876.0 µg/mL, while in antibacterial tests, the ligands showed lower activity compared to streptomycin. SD5 and SD6 compounds, whose activity was determined in vitro studies, were analyzed to elucidate the interaction mechanism with the targets identified in molecular docking studies. Compounds SD5 and SD6 were analyzed in molecular docking studies by interacting with the crystal structures of 5I96 and 6U4J. © Iranian Chemical Society 2026.