Division of Medicinal Chemistry, CSIR-Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001, India.
Bioorg Med Chem Lett. 2013 Sep 15;23(18):5235-8. doi: 10.1016/j.bmcl.2013.06.060. Epub 2013 Jun 29.
A series of substituted aryl pyrimidine derivatives was synthesized and evaluated in vitro for their antileishmanial potential against intracellular amastigotes of Leishmania donovani using reporter gene luciferase assay. Among all, 8 compounds showed promising IC50 values ranging from 0.5 to 12.9 μM. Selectivity indices (S.I.) of all these compounds are far better than reference drugs, sodium stibogluconate (SSG) and miltefosine. On the basis of good S.I., compounds were further screened for their in vivo antileishmanial activity against L. donovani/hamster model. Compounds 2d, 4a and 4b have shown significant inhibition of parasitic multiplication that is 88.4%, 78.1% and 78.2%, respectively at a daily dose of 50 mg/kg × 5 days, when administered intraperitoneally. Compound 2d is most promising one, which may provide a new lead that could be exploited as a new antileishmanial agent.
合成了一系列取代的芳基嘧啶衍生物，并通过报告基因荧光素酶检测法在体外评估它们对利什曼原虫内阿米巴的抗利什曼原虫活性。在所有化合物中，有 8 种化合物表现出有希望的 IC50 值，范围在 0.5 到 12.9 μM 之间。所有这些化合物的选择性指数（S.I.）都远优于参考药物葡萄糖酸锑钠（SSG）和米替福新。基于良好的 S.I.，这些化合物进一步在利什曼原虫/仓鼠模型中进行了体内抗利什曼原虫活性筛选。化合物 2d、4a 和 4b 在每天 50mg/kg×5 天腹腔内给药时，对寄生虫增殖的抑制率分别为 88.4%、78.1%和 78.2%。化合物 2d 是最有前途的一种，它可能提供一个新的先导化合物，可以作为一种新的抗利什曼原虫药物进行开发。
