title: Synthesis, antitumor evaluation and molecular docking studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives.
abstract: A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and evaluated for their antitumor activities. These compounds exhibited potent antiproliferative activities against MCF-7, Bewo and HL-60 cells and c-Met kinase inhibitory activities. Three compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 1.09-2.24μM. Molecular docking was further performed to study the inhibitor-c-Met kinase interactions, and the results show that compound 4j was potently bound to the c-Met kinase with three hydrogen bonds. The further research on acute toxicity and in vivo antitumor activity of compound 4j to ICR (Institute of Cancer Research) mice were carried out, and found 4j with a certain toxicity but good efficacy in vivo. Based on the preliminary results, it is deduced that compound 4j with potent c-Met kinase inhibitory activity may be a potential anticancer agent.
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China. Electronic address: xufeng901@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Yang
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Jun-Rong
authors.initials: JR
authors.lastname: Jiang
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Wan-Gui
authors.initials: WG
authors.lastname: Pan
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Xiao-le
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, PR China.
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.affiliation: ImmuOn Therapeutics, Chenqiao BridgePark, Nantong 226003, PR China.
authors.forename: Qi-Yang
authors.initials: QY
authors.lastname: Shou
authors.affiliation: Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
authors.forename: Han-Gui
authors.initials: HG
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001665:Binding Sites; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008813:Mice, Inbred ICR; D062105:Molecular Docking Simulation; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D006574:Heterocyclic Compounds, 2-Ring; D014230:Triazoles; D019859:Proto-Oncogene Proteins c-met; D019311:Staurosporine
keywords: Antitumor activity; Docking study; Tetrazine; Toxicity; Triazole; X-ray diffraction