title: Synthesis, in vitro and in vivo evaluation of novel substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methyl-quinazolin-4-amines as potent antitumor agents.
abstract: A novel series of substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methylquinazolin-4-amines were synthesized and evaluated for their in vitro antiproliferative activity. Among them, compound 7a exhibited the best potency, with IC50 values of 0.029-0.147 μM against four types of cancer cell lines. In addition, 7a was confirmed that it could arrest the cell cycle at G2/M phase and trigger apoptosis. Indirect immunofluorescence staining revealed its anti-tubulin property. Importantly, 7a significantly inhibited tumor growths in HepG2 xenograft models without causing significant loss of body weight, suggesting that 7a is a promising new anticancer agent to be developed.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Minghai
authors.initials: M
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Taijin
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China. Electronic address: chenlijuan125@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C000612204:N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methyl-quinazolin-4-amine; D010879:Piperazines; D011799:Quinazolines
keywords: 4-Anilinoquinazoline derivatives; Anti-proliferation; G(2)/M arrest