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 electron‐donating 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.