Anti-leishmanial activity of disubstituted purines and related pyrazolo[4,3-d]pyrimidines
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
G0400028
Medical Research Council - United Kingdom
PubMed
21683592
DOI
10.1016/j.bmcl.2011.05.076
PII: S0960-894X(11)00705-0
Knihovny.cz E-resources
- MeSH
- Leishmania donovani drug effects MeSH
- CDC2 Protein Kinase antagonists & inhibitors genetics metabolism MeSH
- Protozoan Proteins antagonists & inhibitors genetics metabolism MeSH
- Purines chemical synthesis chemistry pharmacology MeSH
- Pyrazoles chemistry MeSH
- Pyrimidines chemical synthesis chemistry pharmacology MeSH
- Recombinant Proteins antagonists & inhibitors genetics metabolism MeSH
- Trypanocidal Agents chemical synthesis chemistry pharmacology MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CDC2 Protein Kinase MeSH
- Protozoan Proteins MeSH
- Purines MeSH
- pyrazole MeSH Browser
- Pyrazoles MeSH
- Pyrimidines MeSH
- Recombinant Proteins MeSH
- Trypanocidal Agents MeSH
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.
References provided by Crossref.org
N-Benzyl-9-isopropyl-9H-purin-6-amine
