- Volume 10 Issue 1
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Study on the Effects of Phenyldiazenylanilines on the Activation of Arylhydrocarbon Receptor
Phenyldiazenylaniline 유도체가 방향족탄화수소 수용체의 활성에 미치는 영향
- Received : 2018.11.15
- Accepted : 2019.01.20
- Published : 2019.01.28
AHR regulates the expression of xenobiotics metabolizing enzymes (XMEs) as a transcription fact upon binding of ligands that are mainly aryl hydrocarbons. The role of AHR in human physiology has been intensively investigated for the past decades, however our understanding on AHR yet to be elucidated largely due to the lack of proper chemical agents. It has been demonstrated that AHR correlates to pathogenesis for some diseases in recent studies suggesting that the study on the AHR may provide a valid therapeutic target. Classical antagonists in current use are reported to be partially agonistic whereas a pure antagonist is yet to be found. In this study, phenyldiazenylaniline has been designed based on the structure of two known AHR antagonist, Resveratrol and CH223191. The derivatives of phenyldiazenylaniline have been prepared and subjected to assessment as an AHR antagonist in order to optimize the AHR antagonistic activity of the designed structure by means of convergence study of organic synthesis and molecular biology.
AHR (aryl hydrocarbon receptor);antagonist;phenyldiazenylanline;proper chemical agent;phenyldiazenylaniline;convergence study of chemical structure and biological activity
- K. M. Burbach, A. Poland & C. A. Bradfield. (1992). Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor, Proceedings of the National Academy of Sciences, 89(17), 8185-8189.
- A. B. Okey, D. S. Riddick & P. A. Harper. (1994). Molecular biology of the aromatic hydrocarbon (dioxin) receptor, Trends in Pharmacological Sciences, 15(7), 226-232. https://doi.org/10.1016/0165-6147(94)90316-6
- Ma C., Marlowe J.L., Puga A. (2009) The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways. In: Luch A. (eds) Molecular, Clinical and Environmental Toxicology. Experientia Supplementum, Basel, Birkhauser. DOI : https://doi.org/10.1007/978-3-7643-8336-7_9
- E. J. Choi, D. G. Toscano, J. A. Ryan, N. Riedel & W. A. Toscano, Jr. (1991). Dioxin induces transforming growth factor-alpha in human keratinocytes, The Journal of Biological Chemistry, 266(15), 9591-9597.
- A. Levine-Fridman, L. Chen & C. J. Elferink. (2004). Cytochrome P4501A1 promotes G1 phase cell cycle progression by controlling aryl hydrocarbon receptor activity, Molecular Pharmacology, 65(2), 461-469. https://doi.org/10.1124/mol.65.2.461
- F. Yang & D. Bleich. (2004). Transcriptional regulation of cyclooxygenase-2 gene in pancreatic beta-cells, Journal of Biological Chemistry, 279(34), 35403-35411. https://doi.org/10.1074/jbc.M404055200
- J. Guo, M. Sartor, S. Karyala, M. Medvedovic, S. Kann, A. Puga, P. Ryan & C. R. Tomlinson. (2004). Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice, Toxicology and Applied Pharmacology, 194(1), 79-89. https://doi.org/10.1016/j.taap.2003.09.002
- Y. F. Lu, M. Santostefano, B. D. Cunningham, M. D. (1996). Threadgill and S. Safe, Substituted flavones as aryl hydrocarbon receptor agonists and antagonists, Biochemical Pharmacology, 51(8), 1077-1087. https://doi.org/10.1016/0006-2952(96)00063-9
- J. E. Lee & S. Safe. (2000). 3',4'-dimethoxyflavone as an aryl hydrocarbon receptor antagonist in human breast cancer cells, Toxicological Sciences, 58(2), 235-242. https://doi.org/10.1093/toxsci/58.2.235
- A. Y. Berman, R. A. Metechin, M. Y. Wiesenfeld, M. K. Holz. (2017). The therapeutic potential of resvertrol: a review of clinical trials, NPJ Precision Oncology, 1(1), 35-43. https://doi.org/10.1038/s41698-017-0038-6
- S. H. Kim, E. C. Henry, D. K. Kim, Y. H. Kim, K. J. Shin, M. S. Han, T. G. Lee, J. K. Kang, T. A. Gasiewicz, S. H. Ryu, P. G. Suh. (2006). Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor, Molecular Pharmacology, 69(6), 1871-1878. https://doi.org/10.1124/mol.105.021832
- H. T. Clarke, W. R. Kirner. (1922). Methyl Red, Organic Synthesis, 2, 47-50. https://doi.org/10.15227/orgsyn.002.0047
- J. Reiners, Jr., R. Clift & P. Mathieu. (1999). Suppression of cell cycle progression by flavonoids: dependence on the aryl hydrocarbon receptor, Carcinogenesis, 20(8), 561-1566..
- E. Y. Choi, H. Lee, R. W. Dingle, K. B. Kim & H. I. Swanson. (2012). AHR-based Therapeutic Agents, Molecular and Cellular Pharmacology, 4(2), 53-60.
- S. Kronenberg, C. Esser, & C. Carlberg. (2000). An aryl hydrocarbon receptor conformation acts as the functional core of nuclear dioxin signaling, Nucleic Acids Research. 28(12), 2286-2291. https://doi.org/10.1093/nar/28.12.2286