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

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About: Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://www.sciencedirect.com/science/article/pii/S0223523412003881
Description	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. 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. (en)
Title	Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases (en)
skos:prefLabel	Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases (en)
skos:notation	RIV/61989592:15110/13:33148303!RIV14-GA0-15110___
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(ED0007/01/01), P(GA301/08/1649), P(GAP305/12/0783), Z(AV0Z50380511)
http://linked.open...iv/cisloPeriodika	březen
http://linked.open...vai/riv/dodaniDat	2014
http://linked.open...aciTvurceVysledku	Voller, Jiří
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	109481
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/13:33148303
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Cell cycle; Apoptosis; Cancer; Roscovitine; Inhibitor; Cyclin-dependent kinase (en)
http://linked.open.../riv/klicoveSlovo	Cancer Cyclin-dependent kinase Inhibitor Roscovitine Cell cycle Apoptosis
http://linked.open...odStatuVydavatele	FR - Francouzská republika
http://linked.open...ontrolniKodProRIV	[D3BFC8242EA8]
http://linked.open...i/riv/nazevZdroje	European Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	ED
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	10 (xsd:int)
http://linked.open...vavai/riv/projekt	Evaluation of cyclin-dependent kinase inhibitors in cancer cell lines with specific genetic alterations Centre of the Region Haná for Biotechnological and Agricultural Research Modulation of cell division of normal and cancer cells by cyclin-dependent kinase inhibitors
http://linked.open...UplatneniVysledku	2013
http://linked.open...v/svazekPeriodika	61
http://linked.open...iv/tvurceVysledku	Jorda, Radek Kryštof, Vladimír Pospíšil, Tomáš Strnad, Miroslav Voller, Jiří Zatloukal, Marek Gucký, Tomáš Řezníčková, Eva Adamcová, Helena Malínková, Veronika
http://linked.open...ain/vavai/riv/wos	000316537200006
http://linked.open...n/vavai/riv/zamer	Mechanismy regulace růstu a vývoje rostlin na úrovni buněk, orgánů a celých organismů: fyziologické, genetické a molekulárně biologické základy
issn	0223-5234
number of pages	12 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.ejmech.2012.06.036
http://localhost/t...ganizacniJednotka	15110

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