title: Design, synthesis and biological evaluation of novel pyrazoline-containing derivatives as potential tubulin assembling inhibitors.
abstract: A series of novel pyrazoline-containing derivatives (15-47) has been designed, synthesized and evaluated for their biological activities. Among them, compound 18 displayed the most potent antiproliferative activity against A549, MCF-7 and HepG-2 cells line (IC50 = 0.07 μM, 0.05 μM, 0.03 μM, respectively) and the tubulin polymerization inhibitory activity (IC50 = 1.88 μM), being comparable to CA-4. Furthermore, we also tested that compound 18 was a potent inducer of apoptosis in HepG-2 cells and it had cellular effects typical for microtubule interacting agents, causing accumulation of cells in the G2/M phase of the cell cycle. These studies, along with molecular docking, provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
authors.forename: Yu-jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: School of Medicine, Nanjing University, Nanjing 210093, PR China.
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
authors.forename: Qi-Zhang
authors.initials: QZ
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, PR China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D014404:Tubulin; D050257:Tubulin Modulators
keywords: Molecular docking; Pyrazoline; Tubulin polymerization inhibitors