作为CRK3激酶抑制剂且具有体外抗利什曼原虫活性的2,6,9-三取代嘌呤
2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro.
作者信息
Řezníčková Eva, Popa Alexandr, Gucký Tomáš, Zatloukal Marek, Havlíček Libor, Bazgier Václav, Berka Karel, Jorda Radek, Popa Igor, Nasereddin Abdelmajeed, Jaffe Charles L, Kryštof Vladimír, Strnad Miroslav
机构信息
Laboratory of Growth Regulators & Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Palacký University and Institute of Experimental Botany AS CR, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
Laboratory of Growth Regulators & Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Palacký University and Institute of Experimental Botany AS CR, Šlechtitelů 11, 783 71 Olomouc, Czech Republic; Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 1192/12, 771 46 Olomouc, Czech Republic.
出版信息
Bioorg Med Chem Lett. 2015 Jun 1;25(11):2298-301. doi: 10.1016/j.bmcl.2015.04.030. Epub 2015 Apr 16.
Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model.
在此，我们描述了一个2,6,9-三取代嘌呤文库的杀利什曼原虫活性，该文库经筛选与Cdc2相关蛋白激酶3（CRK3）相互作用，随后检测其对寄生利什曼原虫物种的活性。活性最强的化合物对重组CRK3的IC50值为162 nM，在低微摩尔浓度下对硕大利什曼原虫和杜氏利什曼原虫具有体外活性。使用同源模型通过分子对接研究了其与CRK3的结合模式。
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