A class of carbonic anhydrase IX/XII – selective carboxylate inhibitors

Abstract

A small series of 2,4-dioxothiazolidinyl acetic acids was prepared from thiourea, chloroacetic acid, aromatic aldehydes, and ethyl-2-bromoacetate. They were assayed for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms of human (h) origin, the cytosolic hCA I and II, and the transmembrane hCA IX and XII, involved among others in tumorigenesis (hCA IX and XII) and glaucoma (hCA II and XII). The two cytosolic isoforms were not inhibited by these carboxylates, which were also rather ineffective as hCA IX inhibitors. On the other hand, they showed submicromolar hCA XII inhibition, with K_Is in the range of 0.30–0.93 µM, making them highly CA XII-selective inhibitors.

Keywords:

• Carbonic anhydrase
• inhibitor
• isoform XII
• isoform-selective inhibitor
• carboxylate

Acknowledgements

The authors would like to extend their sincere appreciation to Researchers Supporting Project Number (RSP-2019/50), King Saud University, Riyadh, Saudi Arabia.

Disclosure statement

No potential conflict of interest was reported by the authors.