title: Protolichesterinic acid derivatives: α-methylene-γ-lactones as potent dual activators of PPARγ and Nrf2 transcriptional factors.
abstract: PPARγ and Nrf2 are important transcriptional factors involved in many signaling pathways, especially in the anti-infectious response of macrophages. Compounds bearing a Michael acceptor moiety are well known to activate such transcriptional factors, we thus evaluated the potency of α,β-unsaturated lactones synthesized using fluorous phase organic synthesis. Compounds were first screened for their cytotoxicity in order to select lactones for PPARγ and Nrf2 activation evaluation. Among them, two α-methylene-γ-lactones were identified as potent dual activators of PPARγ and Nrf2 in macrophages.
authors.affiliation: Equipe PNSCM, UMR CNRS 6226, Université de Rennes 1, 2 Avenue du Pr. Léon Bernard, F-35043 Rennes, France; Université de Toulouse III, 118, Route de Narbonne, F-31062 Toulouse Cedex 09, France. Electronic address: anne-cecile.le-lamer@univ-tlse3.fr.
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Le Lamer
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Authier
authors.affiliation: Equipe PNSCM, UMR CNRS 6226, Université de Rennes 1, 2 Avenue du Pr. Léon Bernard, F-35043 Rennes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouaud
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Coste
authors.affiliation: Equipe PNSCM, UMR CNRS 6226, Université de Rennes 1, 2 Avenue du Pr. Léon Bernard, F-35043 Rennes, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Boustie
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
authors.affiliation: Equipe PNSCM, UMR CNRS 6226, Université de Rennes 1, 2 Avenue du Pr. Léon Bernard, F-35043 Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gouault
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D051267:NF-E2-Related Factor 2; D047495:PPAR gamma; C095781:protolichesterinic acid; D015107:4-Butyrolactone
keywords: Michael acceptor; Nrf2; PPARγ; Protolichesterinic acid; α-Methylene-γ-lactones