کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394385 1501157 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates
چکیده انگلیسی

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.

Figure optionsDownload as PowerPoint slideHighlights
► Hybrid furoxanyl N-acylhydrazone derivatives were designed as potential neglected diseases drugs candidates.
► Four compounds were selected for their significant anti-microorganisms activities and selectivities.
► Aspects related to stability and mutagenic effects indicated their potential as drugs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 59, January 2013, Pages 64–74
نویسندگان
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