Synthesis and anti-Trypanosoma cruzi activity of diaryldiazepines

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...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2015-01, Vol.20 (1), p.43-51
Main Authors: Menezes, Júlio César L, Vaz, Luana Beatriz A, de Abreu Vieira, Paula Melo, da Silva Fonseca, Kátia, Carneiro, Cláudia Martins, Taylor, Jason G
Format: Article
Language:English
Subjects:
Animals
Azepines - chemical synthesis
Azepines - chemistry
Azepines - pharmacology
Chagas disease
diaryldiazepines
epimastigote
Magnetic Resonance Spectroscopy
Mass Spectrometry
Pharmaceutical industry
Protozoa
R&D
Research & development
Spectrophotometry, Infrared
Tropical diseases
Trypanocidal Agents - chemical synthesis
Trypanocidal Agents - chemistry
Trypanocidal Agents - pharmacology
Trypanosoma cruzi
Trypanosoma cruzi - drug effects
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules20010043