Potent hydrazone derivatives targeting esophageal cancer cells. 2018

Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China.

Hydrazone and their derivatives are a series of highly active molecules, which are widely used as lead compounds for the research and development of new anti-cancer drugs. In this study, 20 compounds were synthesized, based on this scaffold and their in vitro cytotoxicity against 6 cancer cell lines, including EC9706, SMMC-7721, MCF7, PC3, MGC-803 and EC109 was tested. Among them, compound 6p, showed strong anti-proliferative activities on esophageal carcinoma cells: EC9706 and EC109 with IC50 values of 1.09 ± 0.03 and 2.79 ± 0.45 μM, respectively. 6p also significantly induces both EC9706 and EC109 cell cycle arrest at G0/G1 phase and cell apoptosis, as well as intracellular ROS accumulation, which could be markedly reversed caspase or ROS inhibitor: NAC. Meanwhile, treatment of compound 6p results in significant declined mitochondria membrane potential, increases in the expression of P53 and bax, as well as decrease in Bcl-2. 6p also activates caspase-8/9/3, PARP and Bid, indicating that 6p induces cancer cell apoptosis via the death receptor-mediated extrinsic pathway and the mitochondria-mediated intrinsic pathway. Further studies also proved that 6p does not show obvious side effects at cellular and in vivo levels. Our findings suggested that hydrazone derivative: compound 6p may serve as a lead compound for further optimization against esophageal cancer cells.

UI MeSH Term Description Entries
D004938 Esophageal Neoplasms Tumors or cancer of the ESOPHAGUS. Cancer of Esophagus,Esophageal Cancer,Cancer of the Esophagus,Esophagus Cancer,Esophagus Neoplasm,Neoplasms, Esophageal,Cancer, Esophageal,Cancer, Esophagus,Cancers, Esophageal,Cancers, Esophagus,Esophageal Cancers,Esophageal Neoplasm,Esophagus Cancers,Esophagus Neoplasms,Neoplasm, Esophageal,Neoplasm, Esophagus,Neoplasms, Esophagus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006835 Hydrazones Compounds of the general formula R:N.NR2, as resulting from the action of hydrazines with aldehydes or ketones. (Grant & Hackh's Chemical Dictionary, 5th ed) Hydrazone
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
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D053078 Membrane Potential, Mitochondrial The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP. Delta Psi M,DeltaPsi M,DeltapsiM,Mitochondrial Membrane Potential,Mitochondrial Transmembrane Potential,M, DeltaPsi,Membrane Potentials, Mitochondrial,Mitochondrial Membrane Potentials,Mitochondrial Transmembrane Potentials,Transmembrane Potential, Mitochondrial,Transmembrane Potentials, Mitochondrial
D059447 Cell Cycle Checkpoints Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable. Cell Cycle Arrest,Cell Cycle Control,Cell Cycle Transition Points,Cell Cycle-Transition Points,Arrest, Cell Cycle,Arrests, Cell Cycle,Cell Cycle Arrests,Cell Cycle Checkpoint,Cell Cycle Controls,Cell Cycle-Transition Point,Checkpoint, Cell Cycle,Checkpoints, Cell Cycle,Control, Cell Cycle,Controls, Cell Cycle,Cycle-Transition Point, Cell,Point, Cell Cycle-Transition

Related Publications

Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
May 2016, Biochemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
November 1962, Journal of medicinal and pharmaceutical chemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
March 2009, Bioorganic & medicinal chemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
March 2010, Experimental and therapeutic medicine,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
February 2022, European journal of medicinal chemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
October 2016, European journal of medicinal chemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
February 2021, Journal of medicinal chemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
June 2008, Bioorganic & medicinal chemistry,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
July 2009, Carbohydrate research,
Ling-Yu Li, and Jia-Di Peng, and Wenjuan Zhou, and Hui Qiao, and Xin Deng, and Zhou-Hua Li, and Ji-Deng Li, and Yun-Dong Fu, and Song Li, and Kai Sun, and Hong-Min Liu, and Wen Zhao
November 2022, BMC chemistry,
Copied contents to your clipboard!