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
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