Synthesis, antitumor evaluation and molecular docking studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives
| Autor: | Wan-gui Pan, Jian-yong Wu, Yan Zhu, Feng Xu, Xiao-le Yang, John Wang, Jun-rong Jiang, Han-gui Wu, Zhen-Zhen Yang, Qi-Yang Shou |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stereochemistry Clinical Biochemistry Triazole Pharmaceutical Science Antineoplastic Agents HL-60 Cells Biochemistry Heterocyclic Compounds 2-Ring 03 medical and health sciences chemistry.chemical_compound Tetrazine Inhibitory Concentration 50 Structure-Activity Relationship 0302 clinical medicine In vivo Drug Discovery Animals Humans Molecular Biology Antitumor activity Mice Inbred ICR Binding Sites Chemistry Hydrogen bond Kinase Organic Chemistry Proto-Oncogene Proteins c-met Triazoles Staurosporine Combinatorial chemistry Acute toxicity Molecular Docking Simulation 030104 developmental biology 030220 oncology & carcinogenesis Toxicity MCF-7 Cells Molecular Medicine Drug Screening Assays Antitumor |
| Zdroj: | Bioorganicmedicinal chemistry letters. 26(13) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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