Publications des scientifiques de l'IRD

Hernandez P., Rojas R., Gilman R. H., Sauvain Michel, Lima L. M., Barreiro E. J., Gonzalez M., Cerecetto H. (2013). Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates. European Journal of Medicinal Chemistry, 59, p. 64-74. ISSN 0223-5234.

Titre du document
Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates
Année de publication
2013
Type de document
Article référencé dans le Web of Science WOS:000315554100009
Auteurs
Hernandez P., Rojas R., Gilman R. H., Sauvain Michel, Lima L. M., Barreiro E. J., Gonzalez M., Cerecetto H.
Source
European Journal of Medicinal Chemistry, 2013, 59, p. 64-74 ISSN 0223-5234
Neglected diseases represent a major health problem. It is estimated that one third of the world population is infected with tuberculosis and additionally Leishmaniosis and Chagas disease affect approximately 30 million people. N-Acylhydrazone moiety is a repeated functional group present in several prototypes and drug candidates for these neglected diseases. On the other hand, furoxan system has been studied as pharmacophore for Leishmaniosis and Chagas diseases. Here we report on the design and preparation of forty hybrid furoxanyl N-acylhydrazones and on their activity on Mycobacterium tuberculosis, H37Rv and MDR strains, Trypanosoma cruzi, and Leishmania amazonensis. Among them, four derivatives displayed excellent to good selectivity indexes against the three different microorganisms. Hybrid compound N'-(4-phenyl-3-furoxanylmethylidene)isoniazide 9 showed the best antibacterial profile with MIC value 4.5 lesser than the value for the reference isoniazid against MDR strain. Furoxanyl N-acylhydrazone (E)-2-methyl-N'-(4-phenyl-3-furoxanylmethylidene)-4H-imidazo[1,2-a] pyridine-3-carbohydrazide 15 was ten-fold more potent against T cruzi Amastigotes than the standard drug nifurtimox. On the other hand, derivatives (E)-N'-(5-benzofuroxanylmethylidene)benzo[d][1,3] dioxole-5-carbohydrazide 25 and (E)-N'-(4-hydroxy-3-methoxyphenylmethylidene)-3-methylfuroxan-4-carbohydrazide 37 emerged as leads for the development of new leishmanicidal agents. The adequate stability, in simulated biological system and plasma, and the lack of mutagenicity of these derivatives allow us to propose them as candidates for further pre-clinical studies.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020] ; Santé : généralités [050] ; Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010060725]
Identifiant IRD
fdi:010060725
Contact