Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 22, Pages 10064-10073Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm301201z
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Funding
- Association pour la Recherche sur le Cancer (ARC) [3940, SFI20111204054]
- Conectus
- Fondation pour la Recherche Medicale
- MNESR
- ihu-a-icm
- Federation pour la recherche sur le cenreau
- Carnot Institute Institut du cerveau et de la moelle epiniere - ICM
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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.
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