Anti-leishmanial activity of disubstituted purines and related pyrazolo[4,3-d]pyrimidines

0368593 - ÚEB 2012 RIV GB eng J - Journal Article
Jorda, Radek - Sacerdoti-Sierra, N. - Voller, Jiří - Havlíček, Libor - Kráčalíková, Kateřina - Nowicki, M. W. - Nasereddin, A. - Kryštof, Vladimír - Strnad, Miroslav - Walkinshaw, M. D. - Jaffe, Ch. L.
Anti-leishmanial activity of disubstituted purines and related pyrazolo[4,3-d]pyrimidines.
Bioorganic and Medicinal Chemistry Letters. Roč. 21, č. 14 (2011), s. 4233-4237. ISSN 0960-894X. E-ISSN 1464-3405
R&D Projects: GA ČR GA204/08/0511; GA ČR GA301/08/1649
Institutional research plan: CEZ:AV0Z50380511
Keywords : Leishmania * Cyclin-dependent kinase * Inhibitor * Therapy
Subject RIV: EE - Microbiology, Virology
Impact factor: 2.554, year: 2011

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.
Permanent Link: http://hdl.handle.net/11104/0202892