Hernandez P. auteur aut IRD Rojas R. auteur aut IRD Gilman R. H. auteur aut IRD Sauvain Michel auteur aut IRD Lima L. M. auteur aut IRD Barreiro E. J. auteur aut IRD Gonzalez M. auteur aut IRD Cerecetto H. auteur aut IRD text journalArticle eng text/pdf born digital access 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. specialized N-Acylhydrazone Furoxane Anti-M. tuberculosis Anti-Leishmania Anti-T. cruzi 020 050 052 59 64-74 2013 0223-5234 https://www.documentation.ird.fr/hor/fdi:010060725 10.1016/j.ejmech.2012.10.047 0223-5234 [F B010060725] https://www.documentation.ird.fr/hor/fdi:010060725 https://www.documentation.ird.fr/intranet/publi/2013/04/010060725.pdf Accès réservé (Intranet de l'IRD) IRD - Base Horizon / Pleins textes 2013-05-02 2017-08-23 fdi:010060725 fre