Recherche

Pharmacochimie des Ligands prohibitine: Chimie contre le cancer et les maladies cardiaques et neurologiques

More than 60% of anticancer drugs are of natural origin, or resulting from modifications of natural products. Currently, our main project concerns the medicinal chemistry of flavaglines, a family of plant natural products that display a unique profile of pharmacological properties. Our interest in flavaglines stems from the potency of their cytotoxicity of cancer cells coupled to a lack of toxicity toward non cancer cells. In the course of our research we identified compounds that display enhanced pharmacological properties compared to natural flavaglines. These molecules could improve the efficacy of chemotherapies and alleviate in the same time their adverse effects. With our collaborators, we demonstrated that flavaglines target prohibitins, which are scaffold proteins that modulate many signaling pathways controlling cell survival, metabolism and inflammation. These compounds inhibit also another protein: the translation initiation factor eIF4a.

ELF4

 

With our collaborators in Europe, America and Asia, we are currently pursuing the following objectives:

  • to develop a total synthesis of flavaglines that is both highly flexible and enantiospecific
  • to complete the characterization of the Structure-Activity Relationships (SAR) of flavaglines for their various pharmacological effects
  • to synthesize chemical tools to decipher in detail the action of flavaglines on prohibitin signaling in different physiological and pathological conditions
  • to define the therapeutic potential of flavaglines against cancers, cardiovascular, inflammatory, metabolic and neurological diseases