Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

Zatloukal, M.; Jorda, Radek; Gucký, T.; Řezníčková, Eva; Voller, Jiří; Pospíšil, T.; Malínková, V.; Adamcová, H.; Kryštof, Vladimír; Strnad, Miroslav

doi:https://dx.doi.org/10.1016/j.ejmech.2012.06.036

Number of the records: 1

Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

1.

SYSNO ASEP	0395483
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases
Author(s)	Zatloukal, M. (CZ) Jorda, Radek (UEB-Q)_{ORCID, RID} Gucký, T. (CZ) Řezníčková, Eva (UEB-Q)_{RID, ORCID} Voller, Jiří (UEB-Q)_{RID, ORCID} Pospíšil, T. (CZ) Malínková, V. (CZ) Adamcová, H. (CZ) Kryštof, Vladimír (UEB-Q)_{RID, ORCID} Strnad, Miroslav (UEB-Q)_{RID, ORCID}
Source Title	European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234 Roč. 61, SI (2013), s. 61-72
Number of pages	12 s.
Language	eng - English
Country	FR - France
Keywords	Cyclin-dependent kinase ; Inhibitor ; Roscovitine
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	GAP305/12/0783 GA ČR - Czech Science Foundation (CSF)
	GA301/08/1649 GA ČR - Czech Science Foundation (CSF)
CEZ	AV0Z50380511 - UEB-Q (2005-2011)
UT WOS	000316537200006
DOI	10.1016/j.ejmech.2012.06.036
Annotation	Several inhibitors of cyclin-dependent kinases (CDKs), including the 2,6,9-trisubstituted purine derivative roscovitine, are currently being evaluated in clinical trials as potential anticancer drugs. Here, we describe a new series of roscovitine derivatives that show increased potency in vitro. The series was tested for cytotoxicity against six cancer cell lines and for inhibition of CDKs. For series bearing 2-(hydroxyalkylamino) moiety, cytotoxic potency strongly correlated with anti-CDK2 activity. Importantly, structural changes that increase biochemical and anticancer activities of these compounds also increase elimination half-life. The most potent compounds were investigated further to assess their ability to influence cell cycle progression, p53-regulated transcription and apoptosis. All the observed biological effects were consistent with inhibition of CDKs involved in the regulation of cell cycle and transcription.
Workplace	Institute of Experimental Botany
Contact	David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469
Year of Publishing	2014

Number of the records: 1