Screening of the ICSN chemical and plant extract libraries for the discovery and optimization of natural products targeting kinases and anti-apoptotic proteins – Dedicated to the memory of Pr. François Tillequin

ICSN has a collection of natural compounds and plant extracts thanks to collaborations we have maintained for several years with our colleagues from Africa and Southeast Asia. Screening of these libraries against anti-apoptotic proteins and different protein kinases led to the discovery of new bioactive natural products. From the chemical library, flavonoid alkaloids were thus identified as potent inhibitors of the CDK1 and CDK5 kinases. From the extract library, we have selected several plants whose extracts inhibited the binding of the Bak BH3 peptide to Bcl-xL. The study of these plant species has led to the isolation of a novel chemical series of pentacyclic polyketides and sesquiterpene dimers. Structure, synthesis, molecular modeling and bioactivities will be presented.

Acknowledgments: V. Dumontet, M. Litaudon, B. Morleo, C. Poullain, F. Roussi, T. Sévenet (members of my team), L. Meijer (ManRos Therapeutics, Roscoff), B. Iorga (ICSN, Gif-sur-Yvette), K. Awang (Univ. Kuala Lumpur, Malaysia), N.V. Hung (Institute of Chemistry, Hanoi, Vietnam), P. Rasoanaivo (IMRA, Madagascar), B. Kiremire (Univ. Kampala, Uganda) and colleagues of AFERP (Association Francophone pour l'Enseignement et la Recherche en Pharmacognosy)