Selenolesterase enzyme activity of carbonic anhydrases. Issue 32 (20th March 2020)

• Record Type: Journal Article
• Authors: Angeli, Andrea; Carta, Fabrizio; Donnini, Selene; Capperucci, Antonella; Ferraroni, Marta; Tanini, Damiano; Supuran, Claudiu T.
• Is Part Of: Chemical communications. Volume 56:Issue 32(2020)
• Page Start: 4444
• Page End: 4447
• Publication Date: 2020-03-20
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc00995d
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : An unprecedented carbonic anhydrase-mediated hydrolysis of selenolesters enables the release of selenolates, acting as potent CA inhibitors. A wide range of functionalised selenolesters, smoothly achieved from the corresponding selenols, are studied. Abstract : Carbonic anhydrases (CAs, E.C. 4.2.1.1) are metalloenzymes expressed on a variety of cell types. Their overexpression leads to serious pathologies, including cancer. The discovery of a series of selenolesters with high structural diversity as novel CA inhibitors is reported here. These compounds show remarkable in vitro inhibition against a panel of human CA isoforms such as hCA I, II, IX and XII. We observed that they undergo a CA mediated hydrolysis, releasing different active selenol fragments, which act as CA inhibitors. Notably, to the best of our knowledge, this is the first example of an enzyme with selenolesterase activity. In addition, X-ray crystallographic data support the proposed mechanism, proving selenolesters as novel pro-drug inhibitors with potential pharmacological applications.