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J Enzyme Inhib Med Chem. 2015;30(4):581-5. doi: 10.3109/14756366.2014.956309. Epub 2014 Nov 6.

A new class of quinazoline-sulfonamides acting as efficient inhibitors against the α-carbonic anhydrase from Trypanosoma cruzi.

Author information

1
Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdulaziz University , Al-Kharj , Saudi Arabia .

Abstract

The protozoan parasite Trypanosoma cruzi is the agent responsible for trypanosomiasis (Chagas disease) in humans and other animals. It has been recently reported that this pathogen encodes for an α-class carbonic anhydrase (CA, EC 4.2.1.1), denominated TcCA, which was shown to be crucial for its life cycle. Inhibition studies of a class of 4-oxoquinazoline containing a benzensulfonamide moiety and their 4-thioxo bioisosteres against the protozoan enzyme TcCA are described here. Most of 4-oxoquinazoline sulfonamides showed nanomolar TcCA inhibition activity with K(I)s in the same order of magnitude of acetazolamide (AAZ), whereas their thioxo bioisosters showed moderate anti-Trypanosoma CA potency with K(I)s in the micromolar range. The discovery of compounds incorporating a 4-oxoquinazoline ring as a low-nanomolar TcCA inhibitor is quite promising and it may be useful for developing anti-Trypanosoma agents with a novel mechanism of action compared to the clinically used drugs (such as benznidazole, nifurtimox) for which significant resistance and serious adverse effects due to their high-toxicity appeared.

KEYWORDS:

Trypanosoma cruzi; enzyme inhibitor; quinazoline; sulfonamide; α-Carbonic anhydrase

PMID:
25373503
DOI:
10.3109/14756366.2014.956309
[Indexed for MEDLINE]

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