Diversely substituted sulfamides for fragment-based drug discovery of carbonic anhydrase inhibitors: synthesis and inhibitory profile

Tatiana Sharonova; Petr Zhmurov; Stanislav Kalinin; Alessio Nocentini; Andrea Angeli; Marta Ferraroni; Mikhail Korsakov; Claudiu T Supuran; Mikhail Krasavin

doi:10.1080/14756366.2022.2051023

Diversely substituted sulfamides for fragment-based drug discovery of carbonic anhydrase inhibitors: synthesis and inhibitory profile

J Enzyme Inhib Med Chem. 2022 Dec;37(1):857-865. doi: 10.1080/14756366.2022.2051023.

Authors

Tatiana Sharonova¹, Petr Zhmurov¹, Stanislav Kalinin¹, Alessio Nocentini², Andrea Angeli², Marta Ferraroni², Mikhail Korsakov³, Claudiu T Supuran², Mikhail Krasavin¹

Affiliations

¹ Institute of Chemistry, Saint Petersburg State University, Saint Petersburg, Russia.
² Neurofarba Department, Universita Degli Studi di Firenze, Florence, Italy.
³ Pharmaceutical Technology Transfer Center, Ushinsky Yaroslavl State Pedagogical University, Yaroslavl, Russia.

Abstract

A series of sulfamide fragments has been synthesised and investigated for human carbonic anhydrase inhibition. One of the fragments showing greater selectivity for cancer-related isoforms hCA IX and XII was co-crystalized with hCA II showing significant potential for fragment periphery evolution via fragment growth and linking. These opportunities will be identified in the future via the screening of this fragment structure for co-operative carbonic anhydrase binding with other structurally diverse fragments.[Figure: see text].

Keywords: Carbonic anhydrase; co-operative fragment screening; solubility; sulfamides; zinc-binding groups.

MeSH terms

Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Dose-Response Relationship, Drug
Drug Discovery*
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Molecular Structure
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Carbonic Anhydrase Inhibitors
Isoenzymes
Sulfonamides
Carbonic Anhydrases

Grants and funding

This research was supported by the Ministry of Education of the Russian Federation [government contract 073–00077-21–02 “Development of an innovative glaucoma drug based on selective inhibition of carbonic anhydrase II,” registry number 730000Ф.99.1.БВ10АА00006].