Identification of a New Amide-Containing Thiazole as a Drug Candidate for Treatment of Chagas' Disease

Abstract

ABSTRACTAlthough the parasitic infection Chagas' disease was described over 100 years ago, even now there are not suitable drugs. The available drugs nifurtimox and benznidazole have limited efficacies and tolerances, with proven mutagenic effects. Attempting to find appropriate drugs to deal with this problem, here we report on the development and pharmacological characterization of new amide-containing thiazoles. In the present study, we evaluated thein vitroandin vivoeffects of new candidates againstTrypanosoma cruzi, the etiological agent of Chagas' disease. The lead amide-containing thiazole derivative had potentin vitroactivity, an absence of bothin vitromutagenic andin vivoclastogenic effects, and excellentin vitroselectivity andin vivotolerance. The compound suppressed parasitemia in mice, modifying the anti-T. cruziantibodies like the reference drug, benznidazole, and displayed the lowest mortality among the tested drugs. The present evidence suggests that this compound is a promising anti-T. cruziagent surpassing the lead optimization stage in drug development and leading to a candidate for preclinical study.