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

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.

Graphical Abstract

Keywords:

• Carbonic anhydrase
• zinc-binding groups
• sulfamides
• co-operative fragment screening
• solubility

Acknowledgements

We are grateful to the Research Centre for Magnetic Resonance and the Centre for Chemical Analysis and Materials Research of Saint Petersburg State University Research Park for the analytical data.

Disclosure statement

No potential conflict of interest was reported by all author(s) except CTS. CT Supuran is Editor-in-Chief of the Journal of Enzyme Inhibition and Medicinal Chemistry. He was not involved in the assessment, peer review, or decision-making process of this paper. The authors have no relevant affiliations of financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. This article was submitted before the start of the Russia-Ukraine military conflict on February 24, 2022.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

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].