title: Synthesis, biological evaluation, and molecular docking studies of 2,6-dinitro-4-(trifluoromethyl)phenoxysalicylaldoxime derivatives as novel antitubulin agents.
abstract: A series of 2,6-dinitro-4-(trifluoromethyl)phenoxysalicylaldoxime derivatives (1h-20h) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Among all the compounds, 2h showed the most potent activity in vitro, which inhibited the growth of MCF-7, Hep-G2 and A549 cell lines with IC(50) values of 0.70 ± 0.05, 0.68 ± 0.02 and 0.86 ± 0.05 μM, respectively. Compound 2h also exhibited significant tubulin polymerization inhibitory activity (IC(50)=3.06 ± 0.05 μM). The result of flow cytometry (FCM) demonstrated that compound 2h induced cell apoptosis. Docking simulation was performed to insert compound 2h into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 2h with potent inhibitory activity in tumor growth may be a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Yang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Zhong-Chang
authors.initials: ZC
authors.lastname: Wang
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Gong
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D010091:Oximes; D050257:Tubulin Modulators; D005461:Fluorine; C005704:salicylaldoxime; C023728:acetaldehyde oxime