title: A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions.
abstract: 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 the most potential binding activity. Subsequently, (1)H 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.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Kai-Bo
authors.initials: KB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Da-Hong
authors.initials: DH
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wang
authors.forename: Clement
authors.initials: C
authors.lastname: Lin
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Bai
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Yue-Hu
authors.initials: YH
authors.lastname: Pei
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Yong-Kui
authors.initials: YK
authors.lastname: Jing
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Zhan-Lin
authors.initials: ZL
authors.lastname: Li
authors.forename: Danzhou
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang 110016, Liaoning, P. R. China.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Hua
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001483:Base Sequence; D053898:Biosynthetic Pathways; D002243:Carbolines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D054856:G-Quadruplexes; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D032443:Peganum / Q000737:chemistry* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002243:Carbolines; D009838:Oligodeoxyribonucleotides; D010936:Plant Extracts; C010262:norharman