Inhibition of carbonic anhydrase from Trypanosoma cruzi for the management of Chagas disease: an underexplored therapeutic opportunity.

Abstract:

:An α-carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, a neglected but widespread tropical disease. Inhibition of this α-CAs (TcCA) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. Although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti-T. cruzi activity, due to poor penetration. However, some thiols and hydroxamates acting as low nanomolar TcCA inhibitors also showed significant antitrypanosomal ex vivo activity, making this enzyme an attractive yet underexplored drug target for the management of Chagas disease.

journal_name

Future Med Chem

authors

Supuran CT

doi

10.4155/fmc.15.185

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

311-24

issue

3

eissn

1756-8919

issn

1756-8927

journal_volume

8

pub_type

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