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. 2013

Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
Department of Organic Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, PR China.

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.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011392 Proline A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons. L-Proline,L Proline
D002384 Catalysis The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction. Catalyses
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy

Related Publications

Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
June 2013, Acta crystallographica. Section E, Structure reports online,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
November 2019, Acta crystallographica. Section E, Crystallographic communications,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
April 2024, International journal of molecular sciences,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
August 2014, Archiv der Pharmazie,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
December 2020, Journal of labelled compounds & radiopharmaceuticals,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
May 2014, Acta crystallographica. Section E, Structure reports online,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
October 2014, European journal of medicinal chemistry,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
April 2007, Acta crystallographica. Section C, Crystal structure communications,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
June 2021, Bioorganic & medicinal chemistry letters,
Shu-Qiang Yin, and Min Shi, and Ting-Ting Kong, and Cheng-Mei Zhang, and Kunkun Han, and Biyin Cao, and Zubin Zhang, and Xiaolin Du, and Long-Qian Tang, and Xinliang Mao, and Zhao-Peng Liu
April 2018, Bioorganic chemistry,
Copied contents to your clipboard!