Benzoselenoates: A novel class of carbonic anhydrase inhibitors

Damiano Tanini; Antonella Capperucci; Maria Locuoco; Marta Ferraroni; Gabriele Costantino; Andrea Angeli; Claudiu T Supuran

doi:10.1016/j.bioorg.2022.105751

Benzoselenoates: A novel class of carbonic anhydrase inhibitors

Bioorg Chem. 2022 May:122:105751. doi: 10.1016/j.bioorg.2022.105751. Epub 2022 Mar 22.

Authors

Damiano Tanini¹, Antonella Capperucci¹, Maria Locuoco¹, Marta Ferraroni¹, Gabriele Costantino², Andrea Angeli³, Claudiu T Supuran⁴

Affiliations

¹ University of Florence, Department of Chemistry "Ugo Schiff", Via della Lastruccia 3-13, I-50019, Sesto Fiorentino, Italy.
² Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy.
³ Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, 43124 Parma, Italy; NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: andrea.angeli@unifi.it.
⁴ NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.

PMID: 35344894
DOI: 10.1016/j.bioorg.2022.105751

Abstract

A series of benzoselenoates has been prepared and their inhibitory properties against the most relevant human Carbonic Anhydrases (CAs) isoforms, among which hCA I, II, IV, VII, IX, and XII were investigated. These inhibitors were designed considering the carboxylates and mono-/dithiocarbamates as lead and led to the observation that the COSe^- is a new zinc-binding group (ZBG) for metalloenzymes possessing zinc ions at their active site. The substitution pattern on aromatic ring of the benzoselenoates is the crucial structural element influencing selectivity towards various isoforms. We elucidated the binding mode of benzoselenoates to hCA I and hCA II by using X-ray crystallography. The negatively charged selenium atom from the new ZBG was observed coordinated to the zinc ion from the CA active site at a distance of 2.30-2.40 Å from it. Overall, these data might be useful for the development of new inhibitors with higher selectivity and efficacy for various hCAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbonic Anhydrase Inhibitors* / chemistry
Carbonic Anhydrase Inhibitors* / pharmacology
Carbonic Anhydrases* / metabolism
Catalytic Domain
Humans
Protein Isoforms / metabolism
Structure-Activity Relationship

Substances

Carbonic Anhydrase Inhibitors
Protein Isoforms
Carbonic Anhydrases