iMed-UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6256-60. doi: 10.1016/j.bmcl.2012.07.104. Epub 2012 Aug 15.
Cryptolepine derivatives containing alkyldiamine side-chains, 2, with potent inhibitory activity against Trypanosoma brucei brucei are reported. Compounds 2 showed improved activity and selectivity to T. b. brucei when compared to the lead compound. The most selective compound, 2k, presents a selectivity index value of 6200 and an IC(50) of 10nM against the parasite. These derivatives are also potent inhibitors of the trypanosome papain-like cysteine proteases cruzain, which could, at least in part, explain their antitrypanosomal activity. Overall, these compounds with good antitrypanosomal activity and selectivity provide an encouraging starting point for the rational design of new and effective antitrypanosomal agents.
报道了含有烷二胺侧链的cryptolepine 衍生物 2，对布氏锥虫具有很强的抑制活性。与先导化合物相比，化合物 2 显示出对 T. b. brucei 的活性和选择性提高。最具选择性的化合物 2k 对寄生虫的选择性指数值为 6200，IC50 为 10nM。这些衍生物也是锥虫木瓜蛋白酶样半胱氨酸蛋白酶 cruzain 的有效抑制剂，这至少可以部分解释它们的抗锥虫活性。总的来说，这些具有良好抗锥虫活性和选择性的化合物为合理设计新型有效的抗锥虫药物提供了一个令人鼓舞的起点。
