Novel 2- arylazoimidazole derivatives as inhibitors of Trypanosoma cruzi proliferation: Synthesis and evaluation of their biological activity

ALEJANDRA SALERNO; VIRGINIA LARA; CAROLINA CARRILLO; ALEJANDRA SALERNO; VIRGINIA LARA; CAROLINA CARRILLO; JULIETA LÓPEZ; DARÍO BALCAZAR; MARIA M. BLANCO; JULIETA LÓPEZ; DARÍO BALCAZAR; MARIA M. BLANCO; ANA MARÍA CELENTANO; CARLOS GAOZZA; FERNANDA M. FRANK; ANA MARÍA CELENTANO; CARLOS GAOZZA; FERNANDA M. FRANK

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2017 vol. 125 p. 327 - 334

0223-5234

In this work, the synthesis of a series of 2-arylazoimidazole derivatives 6-20 has been achieved throughthe reaction of imidazole with aryldiazonium salts, followed by ultrasound-assisted alkylation. Thisapproach has important advantages including higher yield, shorter reaction times and milder reactionconditions. The structures of the compounds obtained were determined by MS, IR; and 1H and 13CNMR. The anti-Trypanosoma cruzi activity of the 15 compounds obtained was evaluated. Twocompounds with piperidino substituents in the carboxamide moiety proved to be effective inhibitors ofepimastigote proliferation, obtaining inhibition values comparable to those achieved with the referencedrug Benznidazole. Besides, these compounds displayed low cytotoxicity on mammalian cells. In vivo,both compounds protected mice against a challenge with a lethal Trypanosoma cruzi strain. Theseresults allow us to propose 2-arylazoimidazoles as lead compounds for the design of novel drugs totreat Chagas? disease.