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首页> 外文期刊>Chemical and Pharmaceutical Bulletin >Antileishmanial Thioureas: Synthesis, Biological Activity and in Silico Evaluations of New Promising Derivatives
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Antileishmanial Thioureas: Synthesis, Biological Activity and in Silico Evaluations of New Promising Derivatives

机译：抗leishmanial硫脲：合成，生物活性和新的有希望的衍生物的计算机评价。

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Leishmaniasis is a neglected tropical disease caused by protozoan parasites belonging to the genus Leishmania . Currently, the drugs available for treatment of this disease present high toxicity, along with development of parasite resistance. In order to overcome these problems, efforts have been made to search for new and more effective leishmanicidal drugs. The aim of this study was to synthesize and investigate the leishmanicidal effect of N , N ′-disubstituted thioureas against Leishmania amazonensis , with evaluation of their in silico pharmacokinetics and toxicity profiles. Our results showed that different thioureas could be obtained in high to moderate yields using simple reaction conditions. Nine thiourea derivatives ( 3e , 3i , 3k , 3l , 3p , 3q , 3v , 3x and 3z ) were active against parasite promastigotes (IC50 21.48–189.10?μM), with low cytotoxicity on mice peritoneal macrophages (CC5050=49.22?μM). After that, the most promising thioureas ( 3k , 3l , 3p , 3q and 3v ) showed IC50 ranging from 70 to 150?μM against L. amazonensis amastigotes in infected macrophages. Except for thiourea 3p , the leishmanicidal activity of the derivatives were independent of nitric oxide (NO) production. Thioureas 3q and 3v affected promastigotes cell cycle without disturbing the mitochondrial membrane potential. Furthermore, our derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. These data indicate that thiourea derivatives are good candidates as leading compounds for the development of new leishmanicidal drugs.
机译：利什曼病是由利什曼原虫属的原生动物寄生虫引起的一种被忽视的热带病。当前，可用于治疗该疾病的药物具有高毒性，并伴随着寄生虫抗性的发展。为了克服这些问题，已努力寻找新的和更有效的利什曼杀菌药。这项研究的目的是合成和研究N，N′-二取代的硫脲对亚马逊利什曼原虫的杀菌作用，并评估它们的计算机药代动力学和毒性。我们的结果表明，使用简单的反应条件，可以高到中等的收率获得不同的硫脲。九种硫脲衍生物（3e，3i，3k，3l，3p，3q，3v，3x和3z）对寄生虫前鞭毛体（IC 50 21.48–189.10？M）具有活性，对小鼠腹膜细胞毒性低巨噬细胞（CC 50 50 = 49.22？M）除外。之后，最有前途的硫脲（3k，3l，3p，3q和3v）在感染的巨噬细胞中对亚马氏乳杆菌的IC 50 的范围为70至150μM。除硫脲3p外，这些衍生物的杀菌活性与一氧化氮（NO）的产生无关。硫脲3q和3v在不干扰线粒体膜电位的情况下影响前鞭毛体细胞周期。此外，我们的衍生物显示出令人满意的理论吸收，分布，代谢，排泄，毒性（ADMET）特性。这些数据表明，硫脲衍生物是开发新的杀人为害药物的主要化合物的良好候选者。

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