BIOMAT Database Logo BIOMAT Database Logo

Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation. 2021

Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China.

Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
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
D005260 Female Females
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
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein
D061986 MCF-7 Cells An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.) MCF7 Cells,Michigan Cancer Foundation 7 Cells,Cell, MCF-7,Cell, MCF7,Cells, MCF-7,Cells, MCF7,MCF 7 Cells,MCF-7 Cell,MCF7 Cell
D019869 Phosphatidylinositol 3-Kinases Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell. PI-3 Kinase,Phosphatidylinositol-3-OH Kinase,PtdIns 3-Kinase,PI 3-Kinase,PI-3K,PI3 Kinases,PI3-Kinase,Phosphoinositide 3 Kinases,Phosphoinositide 3-Hydroxykinase,PtdIns 3-Kinases,3-Hydroxykinase, Phosphoinositide,Kinase, PI-3,Kinase, Phosphatidylinositol-3-OH,Kinases, PI3,Kinases, Phosphoinositide 3,PI 3 Kinase,PI3 Kinase,Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 OH Kinase,Phosphoinositide 3 Hydroxykinase,PtdIns 3 Kinase,PtdIns 3 Kinases

Related Publications

Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Rational Design, Synthesis, and Biological Evaluation of 7-Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors.
April 2016, Journal of medicinal chemistry,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Design, synthesis and biological evaluation of novel aminopyrazole- and 7-azaindole-based Nek1 inhibitors and their effects on zebrafish kidney development.
December 2021, Bioorganic & medicinal chemistry letters,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Synthesis and biological evaluation of 7-azaindole derivatives, synthetic cytokinin analogues.
April 2007, Bioorganic & medicinal chemistry letters,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Synthesis and Neuroprotective Biological Evaluation of Quinazolinone Derivatives via Scaffold Hopping.
January 2019, Current organic synthesis,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Discovery of a Novel Series of 7-Azaindole Scaffold Derivatives as PI3K Inhibitors with Potent Activity.
August 2017, ACS medicinal chemistry letters,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Discovery of novel potent PI3K/mTOR dual-target inhibitors based on scaffold hopping: Design, synthesis, and antiproliferative activity.
December 2023, Archiv der Pharmazie,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Design, synthesis and biological evaluation of thrombin inhibitors based on a pyridine scaffold.
August 2007, Organic & biomolecular chemistry,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Synthesis and evaluation of C3 substituted chalcone-based derivatives of 7-azaindole as protein kinase inhibitors.
December 2020, Chemical biology & drug design,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Identification of novel PI3K inhibitors through a scaffold hopping strategy.
November 2017, Bioorganic & medicinal chemistry letters,
Chengbin Yang, and Mingzhu Lu, and Yi Chen, and Ruiqing Xiang, and Tianze Qiu, and Yu Jia, and Yongtai Yang, and Xiaofeng Liu, and Mingli Deng, and Yun Ling, and Yaming Zhou
Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping.
January 2013, European journal of medicinal chemistry,
Copied contents to your clipboard!