title: Synthesis and Biological Evaluation of 1-Methyl-1H-indole-Pyrazoline Hybrids as Potential Tubulin Polymerization Inhibitors.
abstract: A series of 1-methyl-1H-indole-pyrazoline hybrids were designed, synthesized, and biologically evaluated as potential tubulin polymerization inhibitors. Among them, compound e19 [5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide] showed the most potent inhibitory effect on tubulin assembly (IC50 =2.12 μm) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50 values of 0.21-0.31 μm). Further studies confirmed that compound e19 can induce HeLa cell apoptosis, cause cell-cycle arrest in G2 /M phase, and disrupt the cellular microtubule network. These studies, along with molecular docking and 3D-QSAR modeling, provide an important basis for further optimization of compound e19 as a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Ya-Liang
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Dan-Jie
authors.initials: DJ
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Bo-Yan
authors.initials: BY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, P.R. China. zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C000622558:5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide; D000970:Antineoplastic Agents; D007211:Indoles; D011720:Pyrazoles; D014404:Tubulin; D050257:Tubulin Modulators
keywords: apoptosis; indole-pyrazolines; inhibitors; molecular docking; tubulin