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Aryl derivatives of 3H-1,2-benzoxaphosphepine 2-oxides as inhibitors of cancer-related carbonic anhydrase isoforms IX and XII

Authors :
Anastasija Balašova
Aleksandrs Pustenko
Alessio Nocentini
Daniela Vullo
Claudiu T. Supuran
Raivis Žalubovskis
Source :
Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 38, Iss 1 (2023)
Publication Year :
2023
Publisher :
Taylor & Francis Group, 2023.

Abstract

A range of 3H-1,2-benzoxaphosphepine 2-oxide aryl derivatives with various substitution patterns at positions 7, 8, or 9 of the scaffold was synthesised in five steps from the commercially available salicylaldehydes. All of the newly obtained compounds were studied for their inhibition potency against carbonic anhydrase (CA) isoforms I, II, IX, and XII. Delightfully, these compounds showed a striking selectivity for the cancer-associated CA IX and XII over the cytosolic CA I and II, whose inhibition may lead to side-effects. Overall, a structure–activity relationship (SAR) revealed that 7- and 8-substituted aryl derivatives were more effective inhibitors of CA IX and XII than 9-substituted derivatives. In addition, the fluorine-containing analogues emerged as the most potent CA IX/XII inhibitors in this series.

Details

Language :
English
ISSN :
14756366 and 14756374
Volume :
38
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Enzyme Inhibition and Medicinal Chemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.1b617a13ecb413bb5ec49f5b4c2d8f6
Document Type :
article
Full Text :
https://doi.org/10.1080/14756366.2023.2249267