title: Design, synthesis and biological evaluation of millepachine derivatives as a new class of tubulin polymerization inhibitors.
abstract: A series of novel tubulin polymerization inhibitors (9a-9p) have been synthesized and evaluated for their in vitro and in vivo biological activities. Among these compounds, 9e displayed strong antiproliferative activity against several tumor cell lines (IC50=0.15-0.62μM). Compound 9e was also shown to arrest cells in the G2/M phase of the cell cycle and inhibit the polymerization of tubulin. Molecular docking studies suggested that 9e binds into the colchicine binding site of tubulin. In xenograft experiments, 9e exerted more potent anticancer effect than anticancer drug taxol against the H460 Human lung carcinoma in BALB/c nude mice. In summary, these findings suggest that 9e is a promising new antimitotic compound for the potential treatment of cancer.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Han
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Wenshuang
authors.initials: W
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Sang
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D003078:Colchicine / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity
chemical_list: C000588467:8-(3-(4-(diethylamino)phenyl)acryloyl)-2,2-dimethyl-2H-chromen-5-yl propionate; D000970:Antineoplastic Agents; D001578:Benzopyrans; D047188:Chalcones; D014404:Tubulin; D050257:Tubulin Modulators; C583284:millepachine; D003078:Colchicine
keywords: Anticancer; Chalcone; Millepachine; Tubulin