title: Design, synthesis, biological evaluation and molecular modeling of 1,3,4-oxadiazoline analogs of combretastatin-A4 as novel antitubulin agents.
abstract: A total of 20 novel 1,3,4-oxadiazoline analogs (6a-6t) of combretastatin A-4 with naphthalene ring were designed, synthesized, and evaluated for biological activities as potential tubulin polymerization inhibitors. Among these compounds, 6n showed the most potent antiproliferative activities against multiple cancer cell lines and retained the microtubule disrupting effects. Docking simulation was performed to insert compound 6n into the crystal structure of tubulin to determine the probable binding model. These results indicated oxadiazoline compounds bearing the naphthyl moiety are promising tubulin inhibitors.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006860:Hydrogen Bonding; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D013267:Stilbenes / Q000737:chemistry*; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C572005:2-(2'-naphthyl)-5-(2'-naphthyl)-2-acetyl-2,3-dihydro-1,3,4-oxadiazoline; D000970:Antineoplastic Agents; D009281:Naphthalenes; D010069:Oxadiazoles; D010080:Oxazoles; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C058728:fosbretabulin