title: Imidazolone-amide bridges and their effects on tubulin polymerization in cis-locked vinylogous combretastatin-A4 analogues: synthesis and biological evaluation.
abstract: A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c, bearing 3'-NH₂-4'-OCH₃, 4'-CH₃ and 3'-CH₃-substituted 1-phenyl B-ring, confer optimal bioactivity. The binding modes of these compounds to tubulin were obtained by molecular docking, which can explain the compounds' structure-activity relationship. The studies presented here provide a new structural type for the development of novel antitumor agents.
authors.affiliation: Air Force General Hospital, Beijing 100036, China.
authors.forename: Yao-Wu
authors.initials: YW
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Duo
authors.initials: D
authors.lastname: Shi
authors.forename: Xiao-Tian
authors.initials: XT
authors.lastname: Zhou
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Lv
authors.forename: Ju
authors.initials: J
authors.lastname: Zhu
authors.forename: Can-Hui
authors.initials: CH
authors.lastname: Zheng
authors.forename: You-Jun
authors.initials: YJ
authors.lastname: Zhou
mesh_terms: D000577:Amides / Q000737:chemistry*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007536:Isomerism; D013267:Stilbenes / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000577:Amides; D007093:Imidazoles; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C117197:imidazolone; C058728:fosbretabulin