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Synthetic Curcumin Derivatives Inhibit Jun-Fos-DNA Complex Formation

  • Kim, Hyun-Kyung (School of Chemistry, College of Natural Sciences, Seoul National University) ;
  • Yang, Chul-Hak (School of Chemistry, College of Natural Sciences, Seoul National University)
  • 발행 : 2004.12.20

초록

Jun/Fos, a crucial factor in transmitting the tumor-promoting signal from the extracellular environment to the nuclear transcription machinery, has a dimerization interface possessing several coiled structural properties. Jun and Fos can interact with the DNA regulatory region, AP-1 (Activator Protein-1), which is composed of 5'-TGAC/GTCA-3'.$^1$ Curcumin is a well-known anticancer and anti-inflammatory compound.$^{2,3}$ It also acts as an inhibitor of the Jun-Fos function. c-Fos and c-Jun with a bZIP region are overexpressed in BL21 E. coli and purified with an $Ni^{2+}$ affinity column. The inhibitors of Fos-Jun-AP-1 complex formation were searched through the EMSA (electrophoresis mobility shift assay) experiment, and new curcuminoids were synthesized and investigated as to their inhibitory effect on the same system. Two curcuminoids showed a stronger inhibitory effect than curcumin. This inhibitory activity was quantified with EMSA. 1,7-bis(4-methyl)-1,6-heptadiene-3,5-dione (BJC003) and 1,7-bis(4-hydroxy-5-methoxy-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC005) showed remarkably high inhibitory activities. $IC_{50}$ of 1,7-bis(4-methyl)-1,6-heptadiene-3,5-dione (BJC003) and 1,7-bis(4-hydroxy-5-methoxy-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC005) are 8.98 ${\mu}M$ and 5.40 ${\mu}M$, respectively. However, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC004) did not show inhibitory activity.

키워드

참고문헌

  1. Lee, D. K., et al. Anticancer Research 1998, 18, 119-124.
  2. Pabon, H. J. J. Recl. Trav. Chim. Pays-Bas 1964, 83, 379-386.
  3. Toshiya, M.; Akiko, J. J. Agric. Food Chem. 1994, 42, 1850-1856. https://doi.org/10.1021/jf00045a004
  4. Cory, A.; Daniel, L.; Tom, C. Molecular and Cellular Biology 1991, 11, 3624-3632.
  5. Abate, C.; Luk, D.; Gentz, R.; Rauscher, F. J.; Curran, T. Pro.Natl. Acad. Sci. USA 1990, 87, 1032-1036. https://doi.org/10.1073/pnas.87.3.1032
  6. Angel, P. E.; Herrlich, P. A. The Fos and Jun Families ofTranscription Factors; CRC press: U.S.A., 1994; pp 169-286.
  7. Smith, P. K.; Krohn, R. I.; Hermanson, G. T.; Mallia, A. K.;Gartner, F. H.; Provenzano, M. D.; Fujimoto, E. K.; Goeke, N. M.;Olson, B. J.; Klenk, D. C. Anal. Biochem. 1985, 150, 76-85. https://doi.org/10.1016/0003-2697(85)90442-7
  8. Kerppola, T. K.; Curran, T. Cell 1991, 66, 317-326. https://doi.org/10.1016/0092-8674(91)90621-5
  9. Salvatore, S.; Anna, M.; Bruno, M.; Luciano, D. C.; Gabriele, D.;Rocco, D. P.; Francesco, B.; Massimo, L.; Arduino, O.Biochimica et Biophysica Acta 1999, 1430, 103-110. https://doi.org/10.1016/S0167-4838(98)00269-6
  10. Silvia, V.; Alessandra, C.; Jan, N.; Kirk, S.; Mauro, G.; Alberto, V.Protein Expression and Purification 1999, 15, 8-15. https://doi.org/10.1006/prep.1998.0959
  11. Qi, H.; Liping, W.; Michael, F.; Carlos, E. C. The Journal ofBiological Chemistry; 1999, 274, 15305-14314.
  12. Slawomir, D.; Jozef, K. Protein Expression and Purification 1999,16, 96-102. https://doi.org/10.1006/prep.1999.1044
  13. Lullien-Pellerin, V., et al. Eur. J. Biochem. 1999, 260, 861-868. https://doi.org/10.1046/j.1432-1327.1999.00229.x

피인용 문헌

  1. In Silico Inhibition Studies of Jun-Fos-DNA Complex Formation by Curcumin Derivatives vol.2012, pp.2090-2077, 2012, https://doi.org/10.1155/2012/316972
  2. Small Molecule Inhibitors Targeting Activator Protein 1 (AP-1) vol.57, pp.16, 2014, https://doi.org/10.1021/jm5004733
  3. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies vol.11, pp.6, 2016, https://doi.org/10.1371/journal.pone.0156156
  4. Hybridization by an Electrical Force and Electrochemical Genome Detection Using an Indicator-free DNA on a Microelectrode-array DNA Chip vol.26, pp.3, 2004, https://doi.org/10.5012/bkcs.2005.26.3.379
  5. Metallothionein Induces Site-specific Cleavages in tRNAPhe vol.26, pp.6, 2004, https://doi.org/10.5012/bkcs.2005.26.6.921
  6. Curcuminoids Inhibit Multiple Human Cytochromes P450, UDP-Glucuronosyltransferase, and Sulfotransferase Enzymes, whereas Piperine Is a Relatively Selective CYP3A4 Inhibitor vol.36, pp.8, 2008, https://doi.org/10.1124/dmd.108.020552
  7. Mechanism of Small Molecules Inhibiting Activator Protein-1 DNA Binding Probed with Induced Fit Docking and Metadynamics Simulations vol.59, pp.12, 2019, https://doi.org/10.1021/acs.jcim.9b00693
  8. Virtual screening by 2-D fingerprints, shape and docking for discovering new chemotypes of activator protein-1 inhibitors vol.39, pp.7, 2004, https://doi.org/10.1080/07391102.2020.1749130