Anti-leishmanial activity of disubstituted purines and related pyrazolo[4,3-d]pyrimidines
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
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-zdroje
- MeSH
- Leishmania donovani účinky léků MeSH
- proteinkinasa CDC2 antagonisté a inhibitory genetika metabolismus MeSH
- protozoální proteiny antagonisté a inhibitory genetika metabolismus MeSH
- puriny chemická syntéza chemie farmakologie MeSH
- pyrazoly chemie MeSH
- pyrimidiny chemická syntéza chemie farmakologie MeSH
- rekombinantní proteiny antagonisté a inhibitory genetika metabolismus MeSH
- trypanocidální látky chemická syntéza chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- proteinkinasa CDC2 MeSH
- protozoální proteiny MeSH
- puriny MeSH
- pyrazole MeSH Prohlížeč
- pyrazoly MeSH
- pyrimidiny MeSH
- rekombinantní proteiny MeSH
- trypanocidální látky 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.
Citace poskytuje Crossref.org
N-Benzyl-9-isopropyl-9H-purin-6-amine
