2. Academic Validation
  3. Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors

Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors

  • J Nat Prod. 2014 May 23;77(5):1117-22. doi: 10.1021/np400856h.
Mehdi A Beniddir 1,  Erell Le Borgne,  Bogdan I Iorga,  Nadège Loaëc,  Olivier Lozach,  Laurent Meijer,  Khalijah Awang,  Marc Litaudon
Affiliations

Affiliation

  • 1 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.
PMID: 24798019 DOI: 10.1021/np400856h
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.

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