title: Stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc by quindoline derivatives.
abstract: Stabilization of G-quadruplex structures in the promoter region of certain oncogenes is an emerging field in anticancer drug design. Human c-myc gene is one of these oncogenes, and G-quadruplexes have been proven to be the transcriptional controller of this gene. In the present study, the interaction of quindoline derivatives with G-quadruplexes in c-myc was investigated. The experimental results indicated that these derivatives have the ability to induce/stabilize the G-quadruplexes in c-myc, which lead to down-regulation of the c-myc in the Hep G2 cell line. It was found that derivatives with terminal amino groups in their side chains would selectively bind to the isomers with the double nucleotide loops in the absence of K+. Molecular modeling studies revealed the binding mode between the derivatives and the G-quadruplexes is end-stacking at the 3'-position, and the positively charged side chain on the quindoline derivatives may contribute to the selectivity to certain loop isomers of topological quadruplexes as well as the improved stabilization action.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Lu
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Kwok-Yin
authors.initials: KY
authors.lastname: Wong
authors.forename: Johnny Cheuk-On
authors.initials: JC
authors.lastname: Tang
authors.forename: Albert Sun-Chi
authors.initials: AS
authors.lastname: Chan
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D003956:Dialysis; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D007536:Isomerism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D007211:Indoles; D016271:Proto-Oncogene Proteins c-myc; D011804:Quinolines; C016712:quindoline; D006147:Guanine; D004247:DNA