title: Flavaglines: potent anticancer drugs that target prohibitins and the helicase eIF4A.
abstract: Flavaglines are complex natural products that are found in several medicinal plants of Southeast Asia in the genus Aglaia; these compounds have shown exceptional anticancer and cytoprotective activities. This review describes the significance of flavaglines as a new class of pharmacological agents and presents recent developments in their synthesis, structure-activity relationships, identification of their molecular targets and modes of action. Flavaglines display a unique profile of anticancer activities that are mediated by two classes of unrelated proteins: prohibitins and the translation initiation factor eIF4A. The identification of these molecular targets is expected to accelerate advancement toward clinical studies. The selectivity of cytotoxicity towards cancer cells has been shown to be due to an inhibition of the transcription factor HSF1 and an upregulation of the tumor suppressor TXNIP. In addition, flavaglines display potent anti-inflammatory, cardioprotective and neuroprotective activities; however, the mechanisms underlying these activities are yet to be elucidated.
authors.affiliation: Therapeutic Innovation Laboratory (UMR 7200), CNRS/University of Strasbourg, Faculty of Pharmacy, 67401 Illkirch Cedex, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Basmadjian
authors.forename: Frédéric
authors.initials: F
authors.lastname: Thuaud
authors.forename: Nigel
authors.initials: N
authors.lastname: Ribeiro
authors.forename: Laurent
authors.initials: L
authors.lastname: Désaubry
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D039601:Eukaryotic Initiation Factor-4A / Q000187:drug effects*; D006801:Humans; D000091402:Prohibitins; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D000091402:Prohibitins; D012097:Repressor Proteins; D039601:Eukaryotic Initiation Factor-4A