Flavaglines as potent anticancer and cytoprotective agents.

Nigel Ribeiro (1) , Frédéric Thuaud (1) , Yohann Bernard (2) , Christian Gaiddon (3) , Thierry Cresteil (4) , Audrey Hild (5) , Etienne C Hirsch (5) , Patrick Pierre Michel (5) , Canan G Nebigil (2) , Laurent Désaubry (1)

1 LIT - Laboratoire d'Innovation Thérapeutique
2 BSC - Biotechnologie et signalisation cellulaire
3 Laboratoire de signalisation moléculaire et neurodégénerescence
4 ICSN - Institut de Chimie des Substances Naturelles
5 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière

Flavaglines represent a family of plant natural products that display potent anticancer, cardioprotective, and neuroprotective activities. Novel flavagline derivatives were synthesized and examined for their cytotoxicity on a panel of human cancer cell lines, their cardioprotection against doxorubicin-induced apoptosis in cardiomyocytes, and their neuroprotection in culture models of Parkinson's disease and cisplatin-induced neurotoxicity. The structural requirements of flavaglines for cardio- and neuroprotection were for the first time unraveled and appeared to be slightly different from those for cytotoxicity on cancer cells. We provide also the first evidence that flavaglines may alleviate cisplatin-induced neurotoxicity, suggesting a prophylactic potential of these compounds to prevent this frequently encountered adverse effect of cancer chemotherapies.

Domaines: Chimie organique; Cancer

Nigel Ribeiro, Frédéric Thuaud, Yohann Bernard, Christian Gaiddon, Thierry Cresteil, et al.. Flavaglines as potent anticancer and cytoprotective agents.. Journal of Medicinal Chemistry, 2012, 55 (22), pp.10064-73. ⟨10.1021/jm301201z⟩. ⟨hal-00765387⟩