1. Academic Validation
  2. Synthesis, biological evaluation, and molecular modeling of natural and unnatural flavonoidal alkaloids, inhibitors of kinases

Synthesis, biological evaluation, and molecular modeling of natural and unnatural flavonoidal alkaloids, inhibitors of kinases

  • J Med Chem. 2012 Mar 22;55(6):2811-9. doi: 10.1021/jm201727w.
Thanh Binh Nguyen 1 Olivier Lozach Georgiana Surpateanu Qian Wang Pascal Retailleau Bogdan I Iorga Laurent Meijer Françoise Guéritte
Affiliations

Affiliation

  • 1 Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, 91198 Gif-sur-Yvette Cedex, France.
Abstract

The screening of the ICSN chemical library on various disease-relevant protein kinases led to the identification of natural flavonoidal Alkaloids of unknown configuration as potent inhibitors of the CDK1 and CDK5 kinases. We thus developed an efficient and modular synthetic strategy for their preparation and that of analogues in order to determine the absolute configuration of the active natural flavonoidal Alkaloids and to provide further insights on the structure-activity relationships in this series. The structural determinants of the interaction between some flavonoidal Alkaloids with specific kinases were also evaluated using molecular modeling.

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