A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions
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- 作者：Kai-Bo Wang ; Da-Hong Li ; Ping Hu ; Wen-Jing Wang ; Clement Lin ; Jian Wang ; Bin Lin ; Jiao Bai ; Yue-Hu Pei ; Yong-Kui Jing ; Zhan-Lin Li ; Danzhou Yang ; Hui-Ming Hua
- 刊名：Organic Letters
- 出版年：2016
- 出版时间：July 15, 2016
- 年：2016
- 卷：18
- 期：14
- 页码：3398-3401
- 全文大小：345K
- 年卷期：0
- ISSN：1523-7052
文摘
In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by 1H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, 1H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized β-carboline alkaloids, pegaharmines A–D (1–4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using β-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.