title: Pro-apoptotic meiogynin A derivatives that target Bcl-xL and Mcl-1.
abstract: The biological evaluation of a natural sesquiterpene dimer meiogynin A 1, is described as well as that of five non-natural analogues. Although active on a micromolar range on the inhibition of Bcl-xL/Bak and Mcl-1/Bid interaction, meiogynin A 1 is not cytotoxic on three cell lines that overexpress Bcl-xL and Mcl-1. Contrarily, one of its analogues 6 with an inverted configuration on the side chain and an aromatic moiety replacing the cyclohexane ring was active on both target proteins, cytotoxic on a micromolar range and was found to induce apoptosis through a classical pathway.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Sandy
authors.initials: S
authors.lastname: Desrat
authors.affiliation: UMR CNRS 8126, Université Paris-Sud, Institut Gustave Roussy, 114 rue Edouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Pujals
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Colas
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Dardenne
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gény
authors.affiliation: UMR CNRS 8126, Université Paris-Sud, Institut Gustave Roussy, 114 rue Edouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Loëtitia
authors.initials: L
authors.lastname: Favre
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dumontet
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.affiliation: UMR CNRS 8126, Université Paris-Sud, Institut Gustave Roussy, 114 rue Edouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Raphaël
authors.affiliation: UMR CNRS 8126, Université Paris-Sud, Institut Gustave Roussy, 114 rue Edouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Wiels
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, 1 avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D001565:Benzoates; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009281:Naphthalenes; D012717:Sesquiterpenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C548770:meiogynin A; D011065:Poly(ADP-ribose) Polymerases
keywords: Apoptosis; Bcl-xL; Mcl-1; Molecular docking; Sesquiterpene dimer