@article{fdi:010060725,
  title = {{H}ybrid furoxanyl {N}-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates},
  author = {{H}ernandez, {P}. and {R}ojas, {R}. and {G}ilman, {R}. {H}. and {S}auvain, {M}ichel and {L}ima, {L}. {M}. and {B}arreiro, {E}. {J}. and {G}onzalez, {M}. and {C}erecetto, {H}.},
  editor = {},
  language = {{ENG}},
  abstract = {{N}eglected diseases represent a major health problem. {I}t is estimated that one third of the world population is infected with tuberculosis and additionally {L}eishmaniosis and {C}hagas disease affect approximately 30 million people. {N}-{A}cylhydrazone moiety is a repeated functional group present in several prototypes and drug candidates for these neglected diseases. {O}n the other hand, furoxan system has been studied as pharmacophore for {L}eishmaniosis and {C}hagas diseases. {H}ere we report on the design and preparation of forty hybrid furoxanyl {N}-acylhydrazones and on their activity on {M}ycobacterium tuberculosis, {H}37{R}v and {MDR} strains, {T}rypanosoma cruzi, and {L}eishmania amazonensis. {A}mong them, four derivatives displayed excellent to good selectivity indexes against the three different microorganisms. {H}ybrid 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. {F}uroxanyl {N}-acylhydrazone ({E})-2-methyl-{N}'-(4-phenyl-3-furoxanylmethylidene)-4{H}-imidazo[1,2-a] pyridine-3-carbohydrazide 15 was ten-fold more potent against {T} cruzi {A}mastigotes than the standard drug nifurtimox. {O}n 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. {T}he 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.},
  keywords = {{N}-{A}cylhydrazone ; {F}uroxane ; {A}nti-{M}. tuberculosis ; {A}nti-{L}eishmania ; {A}nti-{T}. cruzi},
  booktitle = {},
  journal = {{E}uropean {J}ournal of {M}edicinal {C}hemistry},
  volume = {59},
  numero = {},
  pages = {64--74},
  ISSN = {0223-5234},
  year = {2013},
  DOI = {10.1016/j.ejmech.2012.10.047},
  URL = {https://www.documentation.ird.fr/hor/fdi:010060725},
}