Novel hybrid motifs of 2-(2-pyridinyl)-1H-benzo[d]imidazole-1,2,3-triazole: Synthesis, anticancer assessment, and in silico study

•Novel 1,2,3-triazole-pyridine-benzo[d]imidazole hybrids 12–21 were synthesized.•Structures of new compounds was confirmed by spectral data and elemental analysis.•Cytotoxicity and in vitro anticancer were assessed against human cancerous cell lines.•Compounds 18 and 19 showed higher anticancer activity than other tested compounds.•The anticancer results were compatible with the molecular docking results. A new category of 1,2,3-triazole-pyridine-benzo[d]imidazole hybrids (12–21) were prepared by a Cu(I)-catalyzed Alkyne-Azide Cyclic-addition (CuAAC) procedure known as Click reaction. The terminal alkyne reaction of 1-(prop‑2-yn-1-yl)-2-(2-pyridinyl)-1H-benzo[d]imidazole 1 with aryl-bearing azide 2–12 afforded 1,2,3-triazole-pyridine-benzo[d]imidazole hybrids. The synthesized adducts were analyzed by NMR (1H and 13C), mass spectroscopy, and elemental analyses. As a result of the LDH assay, the desired adducts were examined for several cancer cells, such as breast (MCF7), human cell line (BJ1), hepatocellular carcinoma (HepG2), and human colon (HCT116). Since the cytotoxicity of the desired compounds is mostly stronger than that of their cytotoxicity on normal cells, most of them are good anticancer candidate medications for the liver, colon, and breast compared to doxorubicin. Studies of molecular docking correlate hybrid activity with constant protein-ligand interactions with biological targets, it revealed that derivatives 18 & 19 could stand out with 3 new H-bonds, including Asp363, asn368 and Asp381, and low bind energy, including -9.4 and -9.0 kcal/mol, respectively. [Display omitted]