Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Univ. Central de Venezuela, Caracas, Venezuela.
Univ. Bordeaux, ISM (CNRS-UMR 5255), Talence, France.
Arch Pharm (Weinheim). 2020 May;353(5):e2000002. doi: 10.1002/ardp.202000002. Epub 2020 Mar 16.
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, LC = 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, LC = 4 and 1 µM) were the most active ones against the two Leishmania strains.
一系列新的含硝基咪唑的衍生物是通过 2-[2-(2-甲基-5-硝基-1H-咪唑-1-基)乙硫基]乙醇与各种取代的苯甲酸偶联合成的。用 m-CPBA 处理后，其中 12 种硫醚化合物进一步氧化为它们的砜类似物。所有 26 种合成化合物都被检测了对 Leishmania (V.) braziliensis 和 Leishmania (L.) mexicana 的体外活性，其中一些表现出有效的抗利什曼原虫活性。在所测试的化合物中，儿茶酚衍生物 2-{[2-(2-甲基-5-硝基-1H-咪唑-1-基)乙基]硫基}乙基 3,4-二羟基苯甲酸酯（9a，LC = 13 和 11 µM）和焦儿茶酚衍生物 2-{[2-(2-甲基-5-硝基-1H-咪唑-1-基)乙基]硫基}乙基 3,4,5-三羟基苯甲酸酯（9b，LC = 4 和 1 µM）对两种利什曼原虫株最为有效。
