Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

Author(s): Katia D'Ambrosio*, Claudiu T. Supuran, Giuseppina De Simone*.

Journal Name: Current Medicinal Chemistry

Volume 25 , Issue 39 , 2018

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Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

Keywords: Carbonic anhydrases, parasitic diseases, malaria, leishmaniasis, Chagas disease, protozoa.

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Article Details

Year: 2018
Page: [5266 - 5278]
Pages: 13
DOI: 10.2174/0929867325666180326160121
Price: $58

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PDF: 29