title: Development of an efficient route toward meiogynin A-inspired dual inhibitors of Bcl-xL and Mcl-1 anti-apoptotic proteins.
abstract: The synthesis, on a large scale, with very good yield and er via an efficient strategy, of a chiral 4-substituted 2-cyclohexenone intermediate, was a milestone in the synthesis of seven analogues of meiogynin A, a natural sesquiterpenoid dimer. These compounds were elaborated in ten linear steps. Their binding affinities for Bcl-xL and Mcl-1, two proteins of the Bcl-2 family, overexpressed in various types of cancers, were evaluated. This enabled to further SAR studies en route to the elaboration of potent dual inhibitors of anti-apoptotic proteins of the Bcl-2 family.
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, Université Paris Sud Labex CEBA, 1 av de la Terrasse, 91 198 Gif-sur-Yvette Cedex, France. fanny.roussi@cnrs.fr.
authors: Sandy
authors: S
authors: Desrat
authors: Camille
authors: C
authors: Remeur
authors: Fanny
authors: F
authors: Roussi
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry; D008024:Ligands; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry; 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: D000447:Aldehydes; D051023:BH3 Interacting Domain Death Agonist Protein; D003512:Cyclohexanones; D008024:Ligands; 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; C028215:2-cyclohexen-1-one; C007229:decalin; C116609:3-hydroxybutanal