Anacardic Acids from Knema hookeriana as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions
Autor: | Nicolas Birlirakis, Marc Litaudon, Jérôme Bignon, Vincent Dumontet, Eric Guittet, Gwladys Rivière, Charlotte Gény, Khaljah Awang, Fanny Roussi |
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Přispěvatelé: | Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Agence National de la Recherche (ANR) [ANR-10-JCJC-7021], Labex Program [ANR-10-LABX-25-01], ICSN, CNRS, Malaysian Ministry of Higher Education [UM.C/HIR/MOHE/SC/37], Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS) |
Rok vydání: | 2016 |
Předmět: |
Protein family
Stereochemistry bcl-X Protein Ethyl acetate Pharmaceutical Science Apoptosis Bcl-xL 01 natural sciences Analytical Chemistry chemistry.chemical_compound Knema hookeriana Drug Discovery [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Nuclear Magnetic Resonance Biomolecular Pharmacology Molecular Structure biology 010405 organic chemistry Organic Chemistry Malaysia Acetophenones Resorcinols biology.organism_classification Anacardic Acids 0104 chemical sciences 3. Good health Anacardic acids 010404 medicinal & biomolecular chemistry bcl-2 Homologous Antagonist-Killer Protein Proto-Oncogene Proteins c-bcl-2 Complementary and alternative medicine Biochemistry chemistry Phytochemical Plant Bark biology.protein Molecular Medicine Apoptosis Regulatory Proteins Two-dimensional nuclear magnetic resonance spectroscopy Bcl-2 Homologous Antagonist-Killer Protein BH3 Interacting Domain Death Agonist Protein Myristicaceae |
Zdroj: | Journal of Natural Products Journal of Natural Products, 2016, 79 (4), pp.838-844. ⟨10.1021/acs.jnatprod.5b00915⟩ Journal of Natural Products, American Chemical Society, 2016, 79 (4), pp.838-844. ⟨10.1021/acs.jnatprod.5b00915⟩ |
ISSN: | 1520-6025 0163-3864 |
DOI: | 10.1021/acs.jnatprod.5b00915 |
Popis: | International audience; Proteins of the Bcl-2 family are key targets in anticancer drug discovery. Disrupting the interaction between anti and pro-apoptotic members of this protein family was the approach chosen in this study to restore apoptosis. Thus, a biological screening on the modulation of the Bcl-xL/Bak and Mcl-1/Bid interactions permitted the selection of Knema hookeriana for further phytochemical investigations. The ethyl acetate extract from the stem bark led to the isolation of six new compounds, three acetophenone derivatives (1-3) and three anacardic acid derivatives (4-6), along with four known anacardic acids (7-10) and two cardanols (11, 12). Their structures were elucidated by 1D and 2D NMR analysis in combination with HRMS experiments. The ability of these compounds to antagonize Bcl-xL/Bak and Mcl-1/Bid association was determined, using a protein protein interaction assay, but only anacardic acid derivatives (4-10) exhibited significant binding properties, with K-i values ranging from 0.2 to 18 mu M. Protein ligand NMR experiments further revealed that anacardic acid 9, the most active compound, does not interact with the anti-apoptotic proteins Bcl-xL and Mcl-1 but instead interacts with pro-apoptotic protein Bid. |
Databáze: | OpenAIRE |
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