3H-1,2-Benzoxaphosphepine 2-oxides as selective inhibitors of carbonic anhydrase IX and XII

Abstract

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

• Carbonic anhydrase
• benzoxaphosphepine 2-oxide
• isoform-selective inhibitors
• anti-tumour