Design and synthesis of novel 4-(4-oxo-2-arylthiazolidin-3-yl)benzenesulfonamides as selective inhibitors of carbonic anhydrase IX over I and II with potential anticancer activity

•Novel 4-(4-oxo-2-arylthiazolidin-3-yl)benzenesulfonamides were synthesized.•Compounds were evaluated for carbonic anhydrase inhibitory activity.•Cytotoxicity evaluation was performed against three cancer cell lines.•Hoechst 33258 and AO-EB staining studies were carried out in COLO-205 cells.•Compound 3f was evaluated in the DLA induced solid tumor model in mice.

The novel 4-(4-oxo-2-arylthiazolidin-3-yl)benzenesulfonamide derivatives were designed and synthesized for selective carbonic anhydrase IX (CA IX) inhibitory activity with anticancer potential. In the CA inhibition assay, 3f was found to be the most potent and selective inhibitor of CA IX with inhibitory constant (KI) value of 2.2 nM. Among the synthesized compounds, 3f showed IC50 values of 5.03 μg/ml (cisplatin: 6.56 μg/ml), 5.81 μg/ml (cisplatin: 5.85 μg/ml), and 23.93 μg/ml (cisplatin: 2.75 μg/ml) against COLO-205, MDA-MB-231, and DU-145 cell lines, respectively. At IC50, 3f caused cell shrinkage, nuclear condensation, and nuclear fragmentation events characteristic to apoptosis in the Hoechst 33258 and acridine orange-ethidium bromide staining studies of COLO-205 cells. In the Dalton's lymphoma ascites (DLA) solid tumor model 3f decreased tumor volume by 64.83% (cisplatin: 71.62%), while increase in mean body weight was found to be only 4.09% (cisplatin: 3.47%).

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