Research toward new anticancer molecules: design, synthesis and biological studies of new inhibitors of selected antiapoptotic proteins
This research project is developed through coordination of two networks. The syntheses of the target molecules are performed at the University of Rennes 1 in connection with CSIR-Indian Institute of Chemical Technology Hyderabad, as part of our Indo-French Joint Laboratory, as well as with the Lebanese University, Beirut. The anticancer activities are studied by biologists in Nantes (breast cancer), Caen (ovarian cancer) and Rennes (melanoma). For the design of the targets, molecular modeling/docking studies are performed in Rennes.
Cancer is a major disease still in urgent demand for new drugs. The discovery of new chemical entities able to restore apoptosis selectively on cancer cells is a very promising new approach to anticancer drugs.
Therefore, we develop a fully integrated strategy targeting some of the most important antiapoptotic proteins in the intrinsic pathway, such as Bcl-2, Bcl-xL and Mcl-1, as well as x-IAP. We have also recently discovered a series of molecules able to disrupt the interaction between the propapoptotic protein PUMA from its antiapoptotic counterpart Bcl-xL.
Our present research in this field is dealing mainly with three aspects:
- development of new series of molecules active against the antiaopoptotic proteins from the BcL-2, BcL-xL and McL-1 family.
- development of new series of molecules active against the x-IAP family of proteins.
- development of new potent molecules able to liberate PUMA from Bcl-xL.