Synthesis and leishmanicidal evaluation of sulfanyl- and sulfonyl-tethered functionalized benzoate derivatives featuring a nitroimidazole moiety |
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| Authors: | Miguel Rodríguez Joyce Gutiérrez José Domínguez Philippe A. Peixoto Alexis Fernández Noris Rodríguez Denis Deffieux Luis Rojas Stéphane Quideau Laurent Pouységu Jaime Charris |
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| Affiliation: | 1. Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Univ. Central de Venezuela, Caracas, Venezuela;2. Univ. Bordeaux, ISM (CNRS-UMR 5255), Talence, France;3. Instituto de Biomedicina, Facultad de Medicina, Univ. Central de Venezuela, Caracas, Venezuela;4. Laboratorio de Productos Naturales, Facultad de Farmacia y Bioanálisis, Univ. de Los Andes, Mérida, Venezuela |
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| Abstract: | A series of new nitroimidazole-containing derivatives was synthesized by coupling of 2-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio]ethanol with diversely substituted benzoic acids. Upon treatment with m-CPBA, 12 of these sulfanyl compounds were further oxidized to their sulfonyl analogs. All the 26 synthetic compounds were examined for in vitro activity against Leishmania (V.) braziliensis and Leishmania (L.) mexicana, and some of them displayed an efficient antileishmanial activity. Among the compounds tested, the catecholic derivative 2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]sulfanyl}ethyl 3,4-dihydroxybenzoate ( 9a , LC50 = 13 and 11 µM) and the pyrogallolic derivative 2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]sulfanyl}ethyl 3,4,5-trihydroxybenzoate ( 9b , LC50 = 4 and 1 µM) were the most active ones against the two Leishmania strains. |
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| Keywords: | antiproliferative agents nitroimidazole synthesis |
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