A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors

0399222 - ÚEB 2014 RIV US eng J - Článek v odborném periodiku
Gucký, T. - Jorda, Radek - Zatloukal, M. - Bazgier, V. - Berka, K. - Řezníčková, Eva - Béres, T. - Strnad, Miroslav - Kryštof, Vladimír
A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors.
Journal of Medicinal Chemistry. Roč. 56, č. 15 (2013), s. 6234-6247. ISSN 0022-2623. E-ISSN 1520-4804
Grant CEP: GA ČR GAP305/12/0783; GA ČR GD203/09/H046
Grant ostatní: GA MŠk(CZ) ED0007/01/01; GA MŠk(CZ) ED2.1.00/03.0058; GA MŠk(CZ) EE2.3.20.0017
Program: ED; ED; EE
Výzkumný záměr: CEZ:AV0Z50380511
Klíčová slova: CHRONIC LYMPHOCYTIC-LEUKEMIA * DINACICLIB SCH 727965 * CELL-CYCLE
Kód oboru RIV: ED - Fyziologie
Impakt faktor: 5.480, rok: 2013

The inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation. In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety.
Trvalý link: http://hdl.handle.net/11104/0226634