2. Academic Validation
  3. A novel series of highly potent 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitors

A novel series of highly potent 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitors

  • J Med Chem. 2013 Aug 8;56(15):6234-47. doi: 10.1021/jm4006884.
Tomáš Gucký 1,  Radek Jorda,  Marek Zatloukal,  Václav Bazgier,  Karel Berka,  Eva Řezníčková,  Tibor Béres,  Miroslav Strnad,  Vladimír Kryštof
Affiliations

Affiliation

  • 1 Centre of the Region Haná for Biotechnological and Agricultural Research, Department of Growth Regulators, Faculty of Science, Palacký University, Šlechtitelů 11, 78371 Olomouc, Czech Republic. akrylhydrazid@seznam.cz
PMID: 23829517 DOI: 10.1021/jm4006884
Abstract

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.

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