期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 21, 期 14, 页码 4233-4237出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.05.076
关键词
Leishmania; Cyclin-dependent kinase; Inhibitor; Therapy
资金
- Czech Science Foundation [204/08/0511, 301/08/1649]
- Ministry of Education, Youth and Sports of the Czech Republic [MSM 6198959216]
- European Commission [LSHB-CT-2004-503467]
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- MRC [G0400028] Funding Source: UKRI
- Medical Research Council [G0400028] Funding Source: researchfish
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 1.5-12.4 mu M. Structure-activity relationships for the tested compounds are discussed and related to the lipophilicity of the compounds. (C) 2011 Elsevier Ltd. All rights reserved.
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