Novel 2-arylazoimidazole derivatives as inhibitors of Trypanosoma cruzi proliferation: Synthesis and evaluation of their biological activity.
In this work, the synthesis of a series of 2-arylazoimidazole derivatives 6-20 has been achieved through the reaction of imidazole with aryldiazonium salts, followed by ultrasound-assisted alkylation. This approach has important advantages including higher yield, shorter reaction times and milder reaction conditions. The structures of the compounds obtained were determined by MS, IR; and1H and13C NMR. The anti-Trypanosoma cruzi activity of the 15 compounds obtained was evaluated. Two compounds with piperidino substituents in the carboxamide moiety proved to be effective inhibitors of epimastigote proliferation, obtaining inhibition values comparable to those achieved with the reference drug 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. These results allow us to propose 2-arylazoimidazoles as lead compounds for the design of novel drugs to treat Chagas' disease.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Orgánica, Junín 956, 1113, CABA, Argentina.
Alejandra
A
Salerno
Universidad de Buenos Aires-CONICET, Instituto de Microbiología y Parasitología Médica, IMPaM, Paraguay 2155, 1121, CABA, Argentina; Universidad de Buenos Aires, Departamento de Microbiología, Parasitología e Inmunología, Paraguay 2155, 1121 CABA, Argentina.
Ana M
AM
Celentano
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Orgánica, Junín 956, 1113, CABA, Argentina.
Julieta
J
López
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Orgánica, Junín 956, 1113, CABA, Argentina.
Virginia
V
Lara
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Orgánica, Junín 956, 1113, CABA, Argentina.
Carlos
C
Gaozza
Instituto de Ciencia y Tecnología Dr. César Milstein (ICT Milstein), (CONICET), Saladillo, 2468, CABA, Argentina.
Darío E
DE
Balcazar
Instituto de Ciencia y Tecnología Dr. César Milstein (ICT Milstein), (CONICET), Saladillo, 2468, CABA, Argentina.
Carolina
C
Carrillo
Universidad de Buenos Aires-CONICET, Instituto de Microbiología y Parasitología Médica, IMPaM, Paraguay 2155, 1121, CABA, Argentina; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología, Junín 956, 1113, CABA, Argentina.
Fernanda M
FM
Frank
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Orgánica, Junín 956, 1113, CABA, Argentina. Electronic address: mblanco@ffyb.uba.ar.
María M
MM
Blanco
D000478:Alkylation; D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013010:Sonication; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects*
D007093:Imidazoles; D014344:Trypanocidal Agents; C029899:imidazole
2-Arylazoimidazoles; Biological activity; Chagas' disease; Ultrasound-assisted alkylation