title: Synthesis, biological evaluation, and molecular modeling of natural and unnatural flavonoidal alkaloids, inhibitors of kinases.
abstract: The screening of the ICSN chemical library on various disease-relevant protein kinases led to the identification of natural flavonoidal alkaloids of unknown configuration as potent inhibitors of the CDK1 and CDK5 kinases. We thus developed an efficient and modular synthetic strategy for their preparation and that of analogues in order to determine the absolute configuration of the active natural flavonoidal alkaloids and to provide further insights on the structure-activity relationships in this series. The structural determinants of the interaction between some flavonoidal alkaloids with specific kinases were also evaluated using molecular modeling.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Thanh Binh
authors.initials: TB
authors.lastname: Nguyen
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Georgiana
authors.initials: G
authors.lastname: Surpateanu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Pascal
authors.initials: P
authors.lastname: Retailleau
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001688:Biological Products; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D057075:Enzyme Assays; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011494:Protein Kinases / Q000737:chemistry; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D001688:Biological Products; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D011494:Protein Kinases