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色烯-2-硫酮类似物的分子对接及体外抗利什曼原虫活性评价

Molecular Docking and in Vitro Antileishmanial Evaluation of Chromene-2-thione Analogues.

作者信息

Verma Rajiv Kumar, Prajapati Vijay Kumar, Verma Girijesh Kumar, Chakraborty Deblina, Sundar Shyam, Rai Madhukar, Dubey Vikash Kumar, Singh Maya Shankar

机构信息

Department of Chemistry and Centre of Advanced Study, Faculty of Science, Banaras Hindu University , Varanasi-221005, India.

Infectious Disease Research Laboratory, Institute of Medical Sciences, Banaras Hindu University , Varanasi-221005, India.

出版信息

ACS Med Chem Lett. 2012 Jan 18;3(3):243-7. doi: 10.1021/ml200280r. eCollection 2012 Mar 8.

Abstract

Leishmaniases are an epidemic in various countries, and the parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemists. To meet this challenge, a series of chromene-2-thione derivatives have been synthesized and docked into the active site of trypanothione reductase (TryR) enzyme required for redox balance of the parasite. These were screened on promastigote, axenic amastigote, and intracellular amastigote stages of Leishmania donovani and found to show high levels of antileishmanial activity together with minimal toxicity to human peripheral blood mononuclear cells. Compounds 3b and 3k were found to be the most active among the tested compounds. Although the compounds show moderate antileishmanial activity, they identify a chemical space to design and develop drugs based on these chromene-2-thione derivatives against the Leishmania parasite.

摘要

利什曼病在多个国家呈流行态势,而且该寄生虫对现有药物产生了耐药性。因此,研发针对利什曼原虫的新药是合成有机化学家们的一个开放研究领域。为应对这一挑战,已合成了一系列色烯-2-硫酮衍生物,并将其对接至该寄生虫氧化还原平衡所需的锥虫硫醇还原酶(TryR)的活性位点。这些衍生物在杜氏利什曼原虫的前鞭毛体、无细胞无鞭毛体和细胞内无鞭毛体阶段进行了筛选,结果显示出高水平的抗利什曼原虫活性,同时对人外周血单个核细胞的毒性极小。化合物3b和3k在测试化合物中活性最高。尽管这些化合物显示出中等抗利什曼原虫活性,但它们确定了一个化学空间,可基于这些色烯-2-硫酮衍生物设计和开发针对利什曼原虫的药物。

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