title: Design, synthesis and biological evaluation of 4-anilinoquinazoline derivatives as new c-myc G-quadruplex ligands.
abstract: A series of 4-anilinoquinazoline derivatives were designed and synthesized as novel c-myc promoter G-quadruplex binding ligands. Subsequent biophysical and biochemical evaluation demonstrated that the introduction of aniline group at 4-position of quinazoline ring and two side chains with terminal amino group improved their binding affinity and stabilizing ability to G-quadruplex DNA. RT-PCR assay and Western blot showed that compound 7a could down-regulate transcription and expression of c-myc gene in Hela cells, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene. More importantly, RTCA and colony formation assays indicated that 7a obviously inhibited Hela cells proliferation, without influence on normal primary cultured mouse mesangial cells. Flow cytometric assays suggested that 7a induced Hela cells to arrest in G0/G1 phase both in a time-dependent and dose-dependent manner.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Ai-Chun
authors.initials: AC
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Guo-Tao
authors.initials: GT
authors.lastname: Kuang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Shi-Ke
authors.initials: SK
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China. Electronic address: ceshzs@mail.sysu.edu.cn.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015536:Down-Regulation / Q000187:drug effects; D015195:Drug Design; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008024:Ligands; D016271:Proto-Oncogene Proteins c-myc; D011799:Quinazolines
keywords: 4-Anilinoquinazoline derivatives; Antitumor; G-quadruplex; Transcriptional regulation; c-myc