Antitrypanosomal Activity of 1,2,3-Triazole-Based Hybrids Evaluated Using In Vitro Preclinical Translational Models.

Chagas disease therapy still relies on two nitroderivatives, nifurtimox and benznidazole (Bz), which have important limitations and serious adverse effects. New therapeutic alternatives for this silent disease, which has become a worldwide public health problem, are essential for its control and elimination. In this study, 1,2,3-triazole analogues were evaluated for efficacy against .

Discovery of novel drugs for Chagas disease: is carbonic anhydrase a target for antiprotozoal drugs?

Introduction: Carbonic anhydrase (CA) arose significant interest as a potential new target for Chagas disease since its discovery in in 2013. Benznidazole and Nifurtimox have been used for Chagas disease treatment for 60 years despite all efforts done for obtaining more efficient treatments, acting in the acute and chronic phases of illness, with fewer side effects and resistance induction.

Areas Covered: We discuss the positive and negative aspects of CA (TcCA) studies as a target for developing new drugs.

Why hasn't there been more progress in new Chagas disease drug discovery?

: Chagas disease (CD) is a neglected disease caused by the protozoan parasite . In terms of novel drug discovery, there has been no progress since the 1960s with the same two drugs, benznidazole and nifurtimox, still in use. The complex life cycle, genetic diversity of strains, different sensitivities to the available drugs, as well as little interest from pharmaceutical companies and inadequate methodologies for translating and findings to the discovery of new drugs have all contributed to the lack of progress.

Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease.

This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability.

Design, synthesis, and evaluation of hydroxamic acid derivatives as promising agents for the management of Chagas disease.

Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5-dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA).

Cloning, characterization, and sulfonamide and thiol inhibition studies of an α-carbonic anhydrase from Trypanosoma cruzi, the causative agent of Chagas disease.

An α-carbonic anhydrase (CA, EC 4.2.1.