title: The interaction of telomeric DNA and C-myc22 G-quadruplex with 11 natural alkaloids.
abstract: Telomeric DNA and C-myc22 are DNA G-quadruplex (G4)-forming sequences associated with tumorigenesis. Ligands that can facilitate the formation and increase the stabilization of G4 can halt tumor cell proliferation and have been regarded as potential anti-cancer drugs. In the present study, we have investigated the interaction of 11 natural alkaloids with G4 formed by telomeric DNA and C-myc22 sequences. Our results indicated that sanguinarine (San), palmatine (Pal), and berberine (Beb) of the first series (S1) can induce the formation of G4 as well as increase the stabilization ability. Daurisoline (S2-1), O-methyldauricine (S2-2), O-diacetyldaurisoline (S2-3), daurinoline (S2-4), dauricinoline (S2-5), N,N'-dimethyldauricine iodide (S2-6), and N,N'-dimethyldaurisoline iodide (S2-7) of the second series (S2) showed similar stabilization ability. We found that unsaturated ring C, N(+) positively charged centers, and conjugated aromatic rings are key factors to increase the stabilization ability of S1, and we gave some advice on structure modification to S2 through structure-activity study. Besides, we found San and Pal to be cell cycle blocker in G(1). San was speculated to bind to G4 through intercalation or end stacking.
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Gene Engineering Drugs and Biological Technology College of Life Science, Beijing Normal University, Beijing, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ji
authors.forename: Hongxia
authors.initials: H
authors.lastname: Sun
authors.forename: Huaxi
authors.initials: H
authors.lastname: Zhou
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xiang
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tang
authors.forename: Changqi
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors; D016615:Telomere / Q000235:genetics*; D044366:Transition Temperature
chemical_list: D000470:Alkaloids; D007364:Intercalating Agents; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D019098:Telomerase