Laboratory of Growth Regulators, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
Bioorg Med Chem Lett. 2011 Jul 15;21(14):4233-7. doi: 10.1016/j.bmcl.2011.05.076. Epub 2011 May 27.
We report here results of screening directed to finding new anti-leishmanial drugs among 2,6-disubstituted purines and corresponding 3,7-disubstituted pyrazolo[4,3-d]pyrimidines. These compounds have previously been shown to moderately inhibit human cyclin-dependent kinases. Since some compounds reduced viability of axenic amastigotes of Leishmania donovani, we screened them for interaction with recombinant leishmanial cdc-2 related protein kinase (CRK3/CYC6), an important cell cycle regulator of the parasitic protozoan. Eighteen pairs of corresponding isomers were tested for viability of amastigotes and for inhibition of CRK3/CYC6 kinase activity. Some compounds (9A, 12A and 13A) show activity against amastigotes with EC(50) in a range 1.5-12.4μM. Structure-activity relationships for the tested compounds are discussed and related to the lipophilicity of the compounds.
我们在此报告了在 2,6-取代嘌呤和相应的 3,7-取代吡唑并[4,3-d]嘧啶中筛选新型抗利什曼原虫药物的结果。这些化合物先前已被证明可适度抑制人类细胞周期蛋白依赖性激酶。由于一些化合物降低了利什曼原虫无鞭毛体的活力，我们筛选了它们与重组利什曼 cdc-2 相关蛋白激酶 (CRK3/CYC6) 的相互作用，CRK3/CYC6 是寄生原生动物的重要细胞周期调节剂。测试了十八对相应的异构体对无鞭毛体的活力和对 CRK3/CYC6 激酶活性的抑制作用。一些化合物（9A、12A 和 13A）对无鞭毛体表现出活性，EC50 在 1.5-12.4μM 范围内。讨论了测试化合物的构效关系，并与化合物的亲脂性相关。
