Synthesis, Biological
Evaluation, and Molecular Modeling
of Natural and Unnatural Flavonoidal Alkaloids, Inhibitors of Kinases
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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