title: Pharmacophore-based discovery of triaryl-substituted imidazole as new telomeric G-quadruplex ligand.
abstract: Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Shuo-Bin
authors.initials: SB
authors.lastname: Chen
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Huang
authors.forename: Lin-Kun
authors.initials: LK
authors.lastname: An
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D019295:Computational Biology; D004353:Drug Evaluation, Preclinical; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D012984:Software; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D044366:Transition Temperature
chemical_list: D007093:Imidazoles; D008024:Ligands; C557881:TSIZ01 compound; C029899:imidazole; D019098:Telomerase