Investigation of N-Arylsulfonylimidazole as Novel Scaffold for Anticancer Agents

Abstract

To explore the possibility of isosteric replacement of imidazolidinone moiety of (S)-1-(1-(4-aminobenzoyl) indolin-5-ylsulfonyl)-4-phenylimidazolidin-2-one (1) for the anticancer activity, novel 1-(1-acyl substituted indolin-5-sulfonyl)-4-phenyl-1H-imidazoles 2 were prepared with varying the N-acyl group on the indoline ring and evaluated for their in vitro anticancer activity against six human cancer cell lines (renal ACHN, colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostrate PC-3). Among the analogs prepared, imidazoles with hydrophobic acyl substituents on indoline like cyclohexanecarbonyl (2e, mean 50% growth inhibition [GI50] = 2.29 μM) or benzoyl with electrondonating groups like 4-methoxybenzoyl (2g, mean GI50 = 4.11 μM) and 4-aminobenzoyl (2a, mean GI50 = 4.45 μM) exhibited relatively good cytotoxicity. Although imidazole moiety of arylsulfonylphenylimidazole 2 contains only hydrogen bonding acceptor property without a stereogenic center unlike imidazolidinone analogs, the high level of the activity of 2 proved that the imidazole motif is obviously good isostere of imidazolidinone moiety of arylsulfonylphenylimidazolidinone 1 for the anticancer activity.