0172280 - UEB-Q 20023065 RIV GB eng J - Journal Article
Vermeulen, K. - Strnad, Miroslav - Kryštof, Vladimír - Havlíček, Libor - Van der Aa, A. - Lenjou, M. - Nijs, G. - Rodrigus, I. - Stockman, B. - Van Onckelen, H. - Van Bockstaele, D. R. - Berneman, Z. N.
Antiproliferative effect of plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases.
Leukemia. Roč. 16, č. 3 (2002), s. 299-305. ISSN 0887-6924. E-ISSN 1476-5551
R&D Projects: GA MŠMT OC 844.10
Institutional research plan: CEZ:AV0Z5038910
Keywords : CHEMICAL INHIBITORS * CDK INHIBITORS * PURINE ANALOGS
Subject RIV: CE - Biochemistry
Impact factor: 4.693, year: 2002

In this study, analogues of olomoucine, a previously described plant cytokinin analogue with cyclin-dependent kinase (CDK) inhibitory activity, were investigated for effect on CDK1 and CDK2 and for effect on cell proliferation. Eight new compounds exhibit stronger inhibitory activity on CDK1 and CDK2 and on cell proliferation than olomoucine. Some active compounds showed low inhibition of proliferation of normal myeloid growth. Improvement of inhibitory activity of known compounds with a C6-benzylamino group was brought about by substitution with one hydroxyl. Also, new C2 substituents associated with inhibitory activity on CDK and on cell proliferation are described. There was a significant correlation between effect on CDK and antiproliferative effect on the KG1 and Molt3 cell lines and on primary human lymphocytes, strongly suggesting that at least part of the anti proliferative effect of cytokinin analogues was due to inhibition of CDK activity. Cytokinin analogues induced apoptosis in a time- and concentration-dependent manner and changes in cell cycle distribution.
Permanent Link: http://hdl.handle.net/11104/0069319