Synthesis and Anti-Trypanosoma cruzi Activity of Diaryldiazepines

Molecules

Júlio César L. Menezes¹  Luana Beatriz A. Vaz²  Paula Melo de Abreu Vieira²  Kátia da Silva Fonseca²  Cláudia Martins Carneiro²  Jason G. Taylor¹ 

[1] Departamento de Química, ICEB, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, CEP, Ouro Preto, MG 35400-000, Brazil; E-Mail:;Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, ICEB II, Morro do Cruzeiro, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Brazil; E-Mails:

关键词: diaryldiazepines;    Trypanosoma cruzi;    Chagas disease;    epimastigote;   

DOI  :  10.3390/molecules20010043

来源: mdpi

【 摘 要 】

Chagas disease is a so-called “neglected disease” and endemic to Latin America. Nifurtimox and benznidazole are drugs that have considerable efficacy in the treatment of the acute phase of the disease but cause many significant side effects. Furthermore, in the Chronic Phase its efficiency is reduced and their therapeutic effectiveness is dependent on the type of T. cruzi strain. For this reason, the present work aims to drive basic research towards the discovery of new chemical entities to treat Chagas disease. Differently substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines were synthesized by cyclocondensation of substituted flavones with ethylenediamine and tested as anti-Trypanosoma cruzi candidates. Epimastigotes of the Y strain from T. cruzi were used in this study and the number of parasites was determined in a Neubauer chamber. The most potent diaryldiazepine that reduced epimastigote proliferation exhibited an IC₅₀ value of 0.25 μM, which is significantly more active than benznidazole.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.