A Series of beta-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions

作者：Wang, Kai-Bo; Li, Da-Hong; Hu, Ping; Wang, Wen-Jing; Lin, Clement; Wang, Jian; Lin, Bin; Bai, Jiao; Pei, Yue-Hu; Jing, Yong-Kui; Li, Zhan-Lin^*; Yang, Danzhou^*; Hua, Hui-Ming^*

来源：Organic Letters, 2016, 18(14): 3398-3401.

DOI：10.1021/acs.orglett.6b01560

• STRICTOSIDINE SYNTHASE
• NATURAL-PRODUCTS
• K+ SOLUTION
• PROMOTER ADOPTS
• INSIGHTS
• DRUGS
• SKELETON
• AGENTS
• DIMER
• LOOP

In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)(4) by H-1 NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, H-1 NMR- and bioassay -guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized beta-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 beta-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.

• 出版日期2016-7-15
• 单位沈阳药科大学