title: Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors.
abstract: Two new acridone alkaloids, chlorospermines A and B (1 and 2), were isolated from the stem bark of Glycosmis chlorosperma, together with the known atalaphyllidine (3) and acrifoline (4), by means of bioguided isolation using an in vitro enzyme assay against DYRK1A. Acrifoline (4) and to a lesser extent chlorospermine B (2) and atalaphyllidine (3) showed significant inhibiting activity on DYRK1A with IC50's of 0.075, 5.7, and 2.2 μM, respectively. Their selectivity profile was evaluated against a panel of various kinases, and molecular docking calculations provided structural details for the interaction between these compounds and DYRK1A.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, LabEx CEBA , 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Mehdi A
authors.initials: MA
authors.lastname: Beniddir
authors.forename: Erell
authors.initials: E
authors.lastname: Le Borgne
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.forename: Nadège
authors.initials: N
authors.lastname: Loaëc
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D054831:Acridones / Q000737:chemistry / Q000302:isolation & purification*; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification*; D008296:Malaysia; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D027821:Rutaceae / Q000737:chemistry*; D000097603:Dyrk Kinases
chemical_list: D054831:Acridones; D000470:Alkaloids; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C000591884:chlorospermine A; C000591885:chlorospermine B