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

• DOI: 10.1021/acs.orglett.6b01560
• Publication Date: 2016-06-24T18:08:18Z
• Authors: 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
• Keywords: Peganum harmala; Chirality

In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by (1)H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed most potential activity. Subsequently, NMR- bioassay-guided isolation P. was performed obtain four pairs partially racemized β-carboline alkaloids, pegaharmines A-D (1-4). Their structures absolute configurations were determined extensive analyses, X-ray crystallography, ECD calculations, CD exciton chirality approaches. Interestingly, pegaharmine D (4), which strongest interaction, exhibited significant cytotoxic against three cancer cell lines. This work contributed a practical strategy discovery novel ligands from natural products provided insights using alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.