2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro

0446880 - ÚEB 2016 RIV GB eng J - Journal Article
Řezníčková, Eva - Popa, Alexandr - Gucký, Tomáš - Zatloukal, Marek - Havlíček, Libor - Bazgier, Václav - Berka, K. - Jorda, Radek - Popa, Igor - Nasereddin, A. - Jaffe, Ch. L. - Kryštof, Vladimír - Strnad, Miroslav
2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro.
Bioorganic and Medicinal Chemistry Letters. Roč. 25, č. 11 (2015), s. 2298-2301. ISSN 0960-894X. E-ISSN 1464-3405
R&D Projects: GA MŠMT(CZ) LO1204
Institutional support: RVO:61389030
Keywords : Purine * Cyclin-dependent kinase * Leishmania
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 2.486, year: 2015

Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model.
Permanent Link: http://hdl.handle.net/11104/0248830