title: 9-N-Substituted berberine derivatives: stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc.
abstract: A series of 9-N-substituted berberine derivatives (2a-j) were synthesized and evaluated as a new class of G-quadruplex binding ligands. G-quadruplex of DNA had been proven to be the transcription controller of human c-myc gene. The interaction of 9-N-substituted berberine derivatives with G-quadruplex DNA in c-myc was examined via EMSA, CD spectroscopy, FRET-melting method, PCR-stop assay, competitive dialysis, cell proliferation assay, and RT-PCR assay. The experiment results indicated that these derivatives could selectively induce and stabilize the formation of intramolecular parallel G-quadruplex in c-myc, which led to down-regulation of transcription of the c-myc in the HL60 lymphomas cell line. The related structure-activity relationships were also discussed.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Jin-Qiang
authors.initials: JQ
authors.lastname: Hou
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Lu
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D001483:Base Sequence; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D001599:Berberine; D004247:DNA