Design and Synthesis of New Triazole‐Benzimidazole Derivatives as Potential PRMT5 Inhibitors

Abstract The art of developing potential anticancer molecules involves a reasonable selection of core moiety and tethering with biologically active pharmacophores. We report a library of rationally designed twelve triazole tethered benzimidazole molecules as novel potential inhibitors for cancer. Their synthesis followed a facile copper‐catalysed cycloaddition reaction with good yields. Although in‐silico molecular docking studies of the synthesized compounds with epigenetic protein viz., PRMTs showed inhibition, the compounds bearing amino acid and aryl groups exhibited excellent performance. The potential anticancer activity of the library of molecules are further evaluated in vitro against the selected cancer cell lines (MCF‐7, DU145, PC3 and HepG2) besides methylation assays. In vitro results revealed that the compounds bearing amino acid and aryl groups exhibited better activity and particularly, 3‐CF 3 ‐phenyl derivative (IC 50 =4.11 μm against MCF‐7) exerted prominent anticancer potency against all the tested cell lines. The observed strong anticancer potency of lead compound is supported by its strong binding nature noted in in‐silico molecular docking studies.