3H-1,2-Benzoxaphosphepine 2-Oxides as Selective Inhibitors of Carbonic Anhydrase IX and XII

Journal of Enzyme Inhibition and Medicinal Chemistry 2023
Aleksandrs Pustenko, Anastasija Balašova, Alessio Nocentini, Claudiu T. Supuran, Raivis Žalubovskis

The synthesis of 3H-1,2-benzoxaphosphepine 2-oxides and evaluation of their inhibitory activity against human carbonic anhydrase (hCA) isoforms I, II, IX, and XII are described. The target compounds were obtained via a concise synthesis from commercial salicylaldehydes and displayed low to sub-micromolar inhibition levels against the tumour-associated isoforms hCA IX and XII. All obtained benzoxaphosphepine 2-oxides possess remarkable selectivity for inhibition of hCA IX/XII over the off-target cytosolic hCA isoforms I and II, whose inhibition may lead to side effects.

Keywords
anti-tumour | benzoxaphosphepine 2-oxide | Carbonic anhydrase | isoform-selective inhibitors
DOI
10.1080/14756366.2022.2143496
Hyperlink
https://www.tandfonline.com/doi/full/10.1080/14756366.2022.2143496

Pustenko, A., Balašova, A., Nocentini, A., Supuran, C., Žalubovskis, R. 3H-1,2-Benzoxaphosphepine 2-Oxides as Selective Inhibitors of Carbonic Anhydrase IX and XII. Journal of Enzyme Inhibition and Medicinal Chemistry, 2023, Vol. 38, No. 1, pp.216-224. ISSN 1475-6366. Available from: doi:10.1080/14756366.2022.2143496

Publication language
English (en)