Advances in the Development of Carbonic Anhydrase Inhibitors as New Antiprotozoal Agents

Curr Med Chem. 2023 Oct 31. doi: 10.2174/0109298673249553231018070920. Online ahead of print.

Abstract

Background: Parasitic diseases are a public health problem despite the existence of drugs for their treatment. These treatments have variable efficacy and, in some cases, serious adverse effects. There has been interest in the enzyme carbonic anhydrase (CA) in the last two decades since it is essential in the life cycle of various parasites due to its important participation in processes such as pyrimidine synthesis, HCO3- transport across cell membranes, and the maintenance of intracellular pH and ion transport (Na+, K+, and H+), among others.

Objective: In this review, CA was analyzed as a pharmacological target in etiological agents of malaria, American trypanosomiasis, leishmaniasis, amoebiasis, and trichomoniasis. The CA inhibitors´ design, binding mode, and structure-activity relationship are also discussed.

Conclusion: According to this review, advances in discovering compounds with potent inhibitory activity suggest that CA is a candidate for developing new antiprotozoal agents.

Keywords: Carbonic anhydrase; Entamoeba histolytica; Leishmania spp; Plasmodium spp; Trichomona vaginalis; Trypanosoma cruzi.