Investigation of N ‐Arylsulfonylimidazole as Novel Scaffold for Anticancer Agents

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‐1 H ‐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 [ GI 50 ] = 2.29  μM ) or benzoyl with electron‐donating groups like 4‐methoxybenzoyl ( 2g , mean GI 50  = 4.11  μM ) and 4‐aminobenzoyl ( 2a , mean GI 50  = 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.