Carbonic anhydrases from Trypanosoma and Leishmania as anti-protozoan drug targets. Issue 5 (1st March 2017)

• Record Type: Journal Article
• Authors: Vermelho, Alane B.; Capaci, Giseli R.; Rodrigues, Igor A.; Cardoso, Verônica S.; Mazotto, Ana Maria; Supuran, Claudiu T.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 5(2017)
• Page Start: 1543
• Page End: 1555
• Publication Date: 2017-03-01
• Subjects: Trypanosoma cruzi -- Leishmania spp. -- Anti-infectives -- Carbonic anhydrase -- Inhibitor -- Sulfonamide -- Hydroxamate; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.01.034
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Protozoa ( Leishmania, Trypanosoma ) ↔ Mosquitoes ↔ Human infection CA Inhibitors. Abstract: Trypanosoma cruzi and Leishmania spp. are protozoa of the Trypanosomatidae family, being the etiological agents of two widespread parasitic diseases, Chagas disease and leishmaniasis, respectively. Both parasites are the focus of worldwide research with the aim to find effective and less toxic drugs than the few ones available so far, and for controlling the spread of the diseases. Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α- and β-class were recently identified in these protozoans and several studies suggested that they could be new targets for drug development. Sulfonamide, thiol and hydroxamate inhibitors effectively inhibited the α-CA from T. cruzi (TcCA) and the β-CA from L. donovani chagasi (LdccCA) in vitro, and some of them also showed in vivo efficacy in inhibiting the growth of the parasites in animal models of Chagas disease and leishmaniasis. As few therapeutic options are presently available for these orphan diseases, protozoan CA inhibition may represent a novel strategy to address this stringent health problem.