Flavaglines as potent anticancer and cytoprotective agents.
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.
Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France.
Nigel
N
Ribeiro
Frédéric
F
Thuaud
Yohann
Y
Bernard
Christian
C
Gaiddon
Thierry
T
Cresteil
Audrey
A
Hild
Etienne C
EC
Hirsch
Patrick Pierre
PP
Michel
Canan G
CG
Nebigil
Laurent
L
Désaubry
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D001688:Biological Products; D002316:Cardiotonic Agents; D004317:Doxorubicin; D002945:Cisplatin