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Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates

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dc.contributor.author Hernández, Paola
dc.contributor.author Rojas, Rosario
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Sauvain, Michel Henri Auguste
dc.contributor.author Lima, Lidia .M.
dc.contributor.author Barreiro, Eliezer J.
dc.contributor.author González, Mercedes
dc.contributor.author Cerecetto, Hugo
dc.date.accessioned 2022-01-04T20:29:57Z
dc.date.available 2022-01-04T20:29:57Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/10451
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries European Journal of Medicinal Chemistry
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject N-Acylhydrazone en_US
dc.subject Furoxane en_US
dc.subject Anti-M tuberculosis en_US
dc.subject Anti-Leishmania en_US
dc.subject Anti-T cruzi en_US
dc.title Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.ejmech.2012.10.047
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.06
dc.relation.issn 1768-3254


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