8-Azapurines as new inhibitors of cyclin-dependent kinases
Libor Havlicek1, Kveta Fuksova, Vladimir Krystof
1Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
Abstract:
Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential anticancer drug candidate as one of the first representatives, roscovitine, is passing Phase II clinical trials for cancer and glomerulonephritis. In this article, we describe a novel modification of the purine scaffold influencing CDK2 inhibitory activities as well as anticancer properties in cell lines of different histopathological origin. The introduced N at position 8 of the purine ring generally lowered CDK2 inhibitory activity of new 8-azapurines (1,2,3-triazolo[4,5-d]pyrimidines) in comparison to the model trisubstituted purines, whereas the antiproliferative potential of some derivatives remained very high, reflecting their ability to activate p53 tumor suppressor.
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