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.

Graphical Abstract

Keywords:

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

Disclosure statement

No potential competing interest was reported by all authors 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.

Additional information

Funding

This work has been supported by the European Social Fund within the Project No 8.2.2.0/20/I/008 “Strengthening of PhD students and academic personnel of Riga Technical University and BA School of Business and Finance in the strategic fields of specialization” of the Specific Objective 8.2.2 “To Strengthen Academic Staff of Higher Education Institutions in Strategic Specialization Areas” of the Operational Programme “Growth and Employment”. The work has been also funded by the Latvian Institute of Organic Synthesis under internal student grant IG-2022–07.