Multicomponent synthesis of γ-lactam derivatives and applications as anticancer agents

Résumé

Cancer, the name given to a collection of neoplastic diseases, is the second most important global cause of death. For ages, the treatment of these diseases has been a highly complex process and, although several innovative approaches have been developed and approved for clinical use, today the prevalent general therapies are still a combination of surgery with chemotherapy and/or radiation therapy. Despite the progress made to date, there is still a serious need to find new chemotherapeutical agents that may be able to bind selective targets at a molecular level. In this context, one promising biochemical target is the interaction between p53 transcription factor, which is mutated or has its function lost in 50% of human cancers, and the MDM2 (Murine Double Minute 2) and MDMX (Murine Double Minute X) proteins. Among the different families of molecules with the capability to inhibit MDM2/MDMX-p53 protein-protein interaction, those containing a pyrrolidone core (γ-lactam), have a promising inhibitory capacity and have not been studied so far in deep.