(−)-Neocaryachine, an Antiproliferative Pavine Alkaloid from Cryptocarya laevigata, Induces DNA Double-Strand Breaks

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• 作者：Yuki Suzuki ; Yohei Saito ; Masuo Goto ; David J. Newman ; Barry R. O’Keefe ; Kuo-Hsiung Lee ; Kyoko Nakagawa-Goto
• 刊名：Journal of Natural Products
• 出版年：2017
• 出版时间：January 27, 2017
• 年：2017
• 卷：80
• 期：1
• 页码：220-224
• 全文大小：332K
• ISSN：1520-6025

文摘

Twelve benzylisoquinoline alkaloids, including pavine and phenanthroindolizidine types, were isolated from a MeOH/CH₂Cl₂ extract of Cryptocarya laevigata (stem bark) through bioactivity-guided fractionation for antitumor effects. Selected compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a multidrug-resistant subline. Since more common 2,3,8,9-tetrasubstituted pavine alkaloids, such as crychine (3), exhibit very mild or no cytotoxicity, this compound type has not been well investigated for antitumor activity. Thus, this report is the first discovery of a 7-hydroxylated pavine alkaloid, (−)-neocaryachine (1), to demonstrate strong antiproliferative activity, with IC₅₀ values of 0.06 to 0.41 μM against five tested tumor cell lines, including an MDR subline. Further mechanism of action studies revealed that 1 impacts the cellular S-phase by inducing DNA double-strand breaks.