Acridone Alkaloids from Glycosmis chlorosperma as DYRK1A Inhibitors

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• 作者：Mehdi A. Beniddir ; Erell Le Borgne ; Bogdan I. Iorga ; Nad猫ge Loa毛c ; Olivier Lozach ; Laurent Meijer ; Khalijah Awang ; Marc Litaudon
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：May 23, 2014
• 年：2014
• 卷：77
• 期：5
• 页码：1117-1122
• 全文大小：385K
• 年卷期：v.77,no.5(May 23, 2014)
• ISSN：1520-6025

文摘

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鈥檚 of 0.075, 5.7, and 2.2 渭M, 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.