Coumarins inhibit η-class carbonic anhydrase from Plasmodium falciparum.

Abstract

Coumarins were discovered to act as inhibitors of α-carbonic anhydrases (CAs, EC 4.2.1.1) after undergoing hydrolysis mediated by the esterase activity of the enzyme to the corresponding 2-hydroxycinnamic acids. Other classes of CAs among the eight currently known do not possess esterase activity or this activity was poorly investigated. Hence, we decided to look at the potential of coumarins as inhibitors of the η-CA from the malaria-producing protozoan Plasmodium falciparum, PfaCA. A panel of simple coumarins incorporating hydroxyl, amino, ketone or carboxylic acid ester moieties in various positions of the ring system acted as low to medium micromolar PfaCA inhibitors, whereas their affinities for the cytosolic off-target human isoforms hCA I and II were in a much higher range. Thus, we confirm that η-CAs possess esterase activity and that coumarins effectively inhibit this enzyme. Elaboration of the simple coumarin scaffolds investigated here may probably lead to more effective PfaCA inhibitors.

• Authors: Simone Giovannuzzi, Viviana De Luca, Alessio Nocentini, Clemente Capasso, Claudiu T Supuran
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 37 Issue 1 Pg. 680-685 (Dec 2022) ISSN: 1475-6374 [Electronic] England
• PMID: 35139744 (Publication Type: Journal Article)

Chemical References

• Carbonic Anhydrase Inhibitors
• Coumarins
• Carbonic Anhydrases

Topics

• Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Carbonic Anhydrases (metabolism)
• Coumarins (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Humans
• Molecular Structure
• Plasmodium falciparum (enzymology)
• Structure-Activity Relationship