title: Discovery and molecular modeling of novel 1-indolyl acetate--5-nitroimidazole targeting tubulin polymerization as antiproliferative agents.
abstract: A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a-3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 μM against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 μM. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Sang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Jigar A
authors.initials: JA
authors.lastname: Makawana
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Shashikant B
authors.initials: SB
authors.lastname: Teraiya
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Dan-Jie
authors.initials: DJ
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Xiang-Xiang
authors.initials: XX
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D021281:Quantitative Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D009593:Nitroimidazoles; D014404:Tubulin; D050257:Tubulin Modulators; C052587:4-nitroimidazole
keywords: Docking; Indolyl acetate; Nitroimidazole; Tubulin