Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors

• Main Authors: Beniddir, M.A.A., Le Borgne, E.A., Iorga, B.L.A., Loaëc, N.B.C., Lozach, O.B., Meijer, L.B.C., Awang, K.D., Litaudon, M.A.
• Format: Article
• Published: American Chemical Society 2014
• Subjects: QD Chemistry
• Online Access: http://eprints.um.edu.my/10701/; http://www.scopus.com/inward/record.url?eid=2-s2.0-84901664872&partnerID=40&md5=4dca11a45560165c4a7f967402c60421

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. © 2014 The American Chemical Society and American Society of Pharmacognosy.