Bulletin of the Korean Chemical Society

  • 제32권9호
  • /
  • Pages.3219-3222
  • /
  • 2011
  • /
  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
권호 표지
DOI QR코드

DOI QR Code

Antimicrobial Flavonoid, 3,6-Dihydroxyflavone, Have Dual Inhibitory Activity against KAS III and KAS I

  • Lee, Jee-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Eun-Jung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • 투고 : 2011.06.17
  • 심사 : 2011.07.04
  • 발행 : 2011.09.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Three types of ${\beta}$-ketoacyl acyl carrier protein synthase (KAS) are important for overcoming the bacterial resistance problem. Recently, we reported the discovery of a antimicrobial flavonoid, YKAF01 (3,6-dihydroxyflavone), which exhibits antibacterial activity against Gram-positive bacteria through inhibition of ${\beta}$-ketoacyl acyl carrier protein synthase III (KAS III). In this report, we suggested that YKAF01 can be an inhibitor ${\beta}$-ketoacyl acyl carrier protein synthase I (KAS I) with dual inhibitory activity for KAS I as well as KAS III. KAS I is related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. We performed docking study of Escherichia coli KAS I (ecKAS I) and YKAF01, and determined their binding model. YKAF01 binds to KAS I with high binding affinity ($2.12{\times}10^6$) and exhibited an antimicrobial activity against the multidrug-resistant E. coli with minimal inhibitory concentration (MIC) value of 512 ${\mu}g$/mL. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

키워드

참고문헌

  1. Lu, Y. J.; Zhang, Y. M.; Rock, C. O. Biochem. Cell Biol. 2004, 82, 145. https://doi.org/10.1139/o03-076
  2. Marrakchi, H.; Zhang,Y. M.; Rock, C. O. Biochem. Soc. Trans. 2002, 30, 1050.
  3. White, S. W.; Zheng, J.; Zhang, Y. M.; Rock, C. O. Annu. Rev. Biochem. 2005, 74, 791. https://doi.org/10.1146/annurev.biochem.74.082803.133524
  4. Khandekar, S. S.; Daines, R. A.; Lonsdale, J. T. Curr. Protein Pept. Sci. 2003, 4, 21. https://doi.org/10.2174/1389203033380377
  5. Heath, R. J.; Rock, C. O. J. Biol. Chem. 1996, 3, 10996.
  6. Heath, R. J.; Rock, C. O. Nat. Prod. Rep. 2002, 19, 581. https://doi.org/10.1039/b110221b
  7. von Wettstein-Knowles, P.; Olsen, J. G.; McGuire, K. A.; Henriksen, A. FEBS J. 2006, 273, 695. https://doi.org/10.1111/j.1742-4658.2005.05101.x
  8. Lee, J. Y.; Jeong, K. W.; Shin, S.; Lee, J. U.; Kim, Y. Bioorg. Med. Chem. 2009, 17, 5408. https://doi.org/10.1016/j.bmc.2009.06.059
  9. Jeong, K. W.; Lee, J. Y.; Kang, D. I.; Lee, J. U.; Shin, S. Y.; Kim, Y. J. Nat. Prod. 2009, 72, 719. https://doi.org/10.1021/np800698d
  10. Lee, J. Y.; Jeong, K. W.; Lee, J. U.; Kang, D. I.; Kim, Y. Bioorg. Med. Chem. 2009, 17, 1506. https://doi.org/10.1016/j.bmc.2009.01.004
  11. Lee, J. Y.; Jeong, K. W.; Lee, J. U.; Kang, D. I.; Kim, Y. Bull. Korean Chem. Soc. 2011, 32, in press.
  12. Price, A. C.; Choi, K. H.; Heath, R. J.; Li, Z.; White, S. W.; Rock, C. O. J. Biol. Chem. 2001, 276, 6551. https://doi.org/10.1074/jbc.M007101200
  13. Macnaughtan, M. A.; Kamar, M.; Alvarez-Manilla, G.; Venot, A.; Glushka, J.; Pierce, J. M.; Prestegard, J. H. J. Mol. Biol. 2007, 366, 1266. https://doi.org/10.1016/j.jmb.2006.12.015
  14. Jayasuriya, H.; Herath, K. B.; Zhang, C.; Zink, D. L.; Basilio, A.; Genilloud, O.; Diez, M. T.; Vicente, F.; Gonzalez, I.; Salazar, O.; Pelaez, F.; Cummings, R.; Ha, S.; Wang, J.; Singh, S. B. Angew. Chem. Int. Ed Engl. 2007, 46, 4684. https://doi.org/10.1002/anie.200701058
  15. Wang, J.; Kodali S.; Lee, S. H.; Galgoci, A.; Painter, R.; Dorso, K.; Racine, F.; Motyl, M.; Hernandez, L.; Tinney, E.; Colletti, S. L.; Herath, K.; Cummings, R.; Salazar, O.; González, I.; Basilio, A.; Vicente, F.; Genilloud, O.; Pelaez, F.; Jayasuriya, H.; Young, K.; Cully, D. F.; Singh, S. B. Proc. Natl. Acad. Sci. 2007, 104, 7612. https://doi.org/10.1073/pnas.0700746104

피인용 문헌

  1. Antibacterial activity of flavonoids and their structure-activity relationship: An update review pp.0951418X, 2018, https://doi.org/10.1002/ptr.6208
  2. Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids vol.13, pp.5, 2011, https://doi.org/10.3390/pharmaceutics13050660