کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1372775 | 981881 | 2011 | 5 صفحه PDF | دانلود رایگان |
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 EC50 in a range 1.5–12.4 μM. Structure–activity relationships for the tested compounds are discussed and related to the lipophilicity of the compounds.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 14, 15 July 2011, Pages 4233–4237