Preparation of S14161 and its analogues and the discovery of 6-bromo-8-ethoxy-3-nitro-2H-chromene as a more potent antitumor agent in vitro
| Autor: | Xinliang Mao, Kunkun Han, Xiaolin Du, Min Shi, Zhao-Peng Liu, Shu-Qiang Yin, Ting-Ting Kong, Cheng-Mei Zhang, Zubin Zhang, Long-Qian Tang, Biyin Cao |
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| Rok vydání: | 2013 |
| Předmět: |
Proline
Stereochemistry Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Neovascularization Physiologic Antineoplastic Agents Biochemistry Umbilical vein Catalysis Piperazines chemistry.chemical_compound Phosphatidylinositol 3-Kinases Cell Movement Cell Line Tumor Drug Discovery Human Umbilical Vein Endothelial Cells Humans Benzopyrans Binding site Phosphorylation Molecular Biology Triethylamine PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Binding Sites Chemistry Cell growth Organic Chemistry In vitro Protein Structure Tertiary Molecular Docking Simulation Apoptosis Molecular Medicine Drug Screening Assays Antitumor Proto-Oncogene Proteins c-akt |
| Zdroj: | Bioorganicmedicinal chemistry letters. 23(11) |
| ISSN: | 1464-3405 |
| Popis: | The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of the phosphoinositide 3-kinase (PI3K). In the present study, we designed a novel synthesis of S14161 and prepared a series of its analogues via the oxa-Michael–Henry reaction in the presence of catalytic amounts of l -proline and triethylamine. Further structural simplification led to the identification of 6-bromo-8-ethoxy-3-nitro-2H-chromene (BENC-511) that exhibited potent antiproliferative activities against a panel of 12 tumor cell lines. Compared with S14161, BENC-511 was more potent in blocking the AKT phosphorylation and inducing cancer cell apoptosis. BENC-511 also displayed more potent effects on human umbilical vein epithelial cells (HUVEC) migration, suggesting its anti-angiogenesis activity. |
| Databáze: | OpenAIRE |
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