Potential 2,4-dimethyl-1H-pyrrole-3-carboxamide bearing benzimidazole template: Design, synthesis, in vitro anticancer and in silico ADME study

Among the novel series of compound, 5-(1H-benzo[d]imidazol-2-yl)-N-(1-cyclohexylethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (8f) exhibited the best growth inhibition against MDA-MB-435 cell line of melanoma (62.46%) at 10 µM concentration. Further computational ADME study qualified its significant physicochemical, pharmacokinetic and drug-likeness properties with good predicted oral bioavailability. [Display omitted] •A series of 2,4-dimethylpyrrole conjugates bearing benzimidazole ring were synthesized.•All derivatives were evaluated for in vitro anticancer activity against NCI-60 panel.•Compound 8f at 10 µM concentration showed 62.46% GI against MDA-MB-435.•In silico ADME evaluation of potent pyrrole-benzimidazole conjugate.•Good drug-likeness and bioactivity scores of potent pyrrole-benzimidazole conjugate. A new series of 2,4-dimethyl-1H-pyrrole-3-carboxamide derivatives bearing benzimidazole moiety was synthesized through a molecular hybridization approach and evaluated for in vitro anticancer activity by NCI-60 on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines at a single dose (10 µM). Among all the synthesized conjugates, some derivatives showed more or less good activity even at such a small dose, while, compound 5-(1H-benzo[d]imidazol-2-yl)-N-(1-cyclohexylethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (8f) displayed significant antiproliferative activity specifically against MDA-MB human cancer cell lines. Compound 8f showed promising activity against MDA-MB-435 cell line of melanoma (Growth inhibition: 62.46%) and MDA-MB-468 cell line of breast (Growth inhibition: 40.24%). Computational ADME study qualified its significant physicochemical, pharmacokinetic and drug-likeness properties with good predicted oral bioavailability. Thus this new hybrid molecules would be useful for further anticancer drug development.