Novel benzoyl thioureido benzene sulfonamides as highly potent and selective inhibitors of carbonic anhydrase IX: optimization and bioactive studies.

CA IX has attracted much attention as a promising target for the development of new anticancer agents. In this study, a series of sulfonamide derivatives were designed and synthesized as potential CA IX inhibitors from a lead compound (benzoyl thioureido benzene sulfonamide) discovered by virtual screening. The bioassay demonstrated that some of the synthesized compounds exhibited potent inhibitory activity against CA IX in the subnanomolar range and high selectivity over isozymes CA I and CA II. Among them, compound 6a displayed inhibitory activity against CA IX with an IC(50) value of 0.48 nM and about 1500-fold selectivity over CA II. The structure-activity relationship and CA IX selectivity of the new sulfonamide derivatives were also analyzed by molecular docking.