New Insights into Conformationally Restricted Carbonic Anhydrase Inhibitors

Molecules. 2023 Jan 16;28(2):890. doi: 10.3390/molecules28020890.

Abstract

This paper reports an investigation into the impact of pyridyl functional groups in conjunction with hydroxide-substituted benzenesulfonamides on the inhibition of human carbonic anhydrase (CA; EC 4.2.1.1) enzymes. These compounds were tested in vitro of CA II and CA IX, two physiologically important CA isoforms. The most potent inhibitory molecules against CA IX, 3g, 3h, and 3k, were studied to understand their binding modes via X-ray crystallography in adduct with CA II and CA IX-mimic. This research further adds to the field of CA inhibitors to better understand ligand selectivity between isoforms found in humans.

Keywords: X-ray crystallography; carbonic anhydrase IX; structure activity relationships.

MeSH terms

  • Antigens, Neoplasm / chemistry
  • Carbonic Anhydrase IX / metabolism
  • Carbonic Anhydrase Inhibitors* / chemistry
  • Carbonic Anhydrases* / chemistry
  • Humans
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • Antigens, Neoplasm

Grants and funding

Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.4-Call for tender No. 3277 of 30 December 2021 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU.