Nitroimidazoles Part 9. Synthesis, molecular docking, and anticancer evaluations of piperazine-tagged imidazole derivatives

Abstract: New piperazine-tagged imidazole derivatives were synthesized via reaction of 1-alkyl/aryl-5-bromo- 2-alkyl-4-nitro-1H-imidazoles 1?3 with piperazine nucleophiles. Nine selected compounds were assessed for their antiproliferative inhibition potency against five human cancer cell lines (MCF-7, PC3, Du145, HepG2 and Dermal/ Fibroblast). Compounds 7 and 10 are the most potent anticancer agents on HepG2 cell line with IC50 values of (5.6 ? 0.5 ?m) and (29.6 ? 7.6 ?m) respectively, and on MCF-7 with IC50 values of (32.1 ? 5.6 ?m) and (46.2 ? 8.2 ?m) respectively. The molecular docking of compounds 7 and 10 has been studied, and the results reveal that the newly designed piperazine-tagged imidazole derivatives bind to the hydrophobic pocket and polar contact with high affinity.