QUERCETIN DERIVATIVES DOCKING BASED ON STUDY OF FLAVONOIDS INTERACTION TO CYCLOOXYGENASE-2

https://doi.org/10.22146/ijc.21545

Rahmana Emran Kartasasmita(1*), Rina Herowati(2), Nuraini Harmastuti(3), Tutus Gusdinar(4)

(1) School of Pharmacy, Bandung Institute of Technology, Jl. Ganesha 10 Bandung 40132
(2) School of Pharmacy, Bandung Institute of Technology, Jl. Ganesha 10 Bandung 40132
(3) Faculty of Pharmacy, Setia Budi University, Jl. Letjen Sutoyo Solo 57127
(4) School of Pharmacy, Bandung Institute of Technology, Jl. Ganesha 10 Bandung 40132
(*) Corresponding Author

Abstract


Due to their ability to inhibit cyclooxygenase-2 (COX-2), certain flavonoids show anti-inflammatory effects. Quercetin is a flavonoid suitable to be chosen as the lead compound for development of safe anti-inflammatory agent, because in addition to its anti-inflammatory effect, quercetin shows also protective effect in gastrointestinal track. The objective of this research is to study the binding modes of certain flavonoids and predict the quercetin derivatives inhibiton activity on COX-2 by means of docking method using ArgusLab 4.0.1 software. Some flavonoids (7-hydroxyflavone, apigenin, galangin, kaempferol, quercetin, naringenin and daidzein) and quercetin derivatives were used as ligands for docking study. The COX-2 structure was obtained from Brookhaven protein databank. After assigning hydrogen atoms and charges, computational docking was performed. The docking results were evaluated based on the binding energy and hydrogen bonding of  the ligands on binding site of COX-2. A curve constructed by plotting binding energy versus logarithm of IC50 of flavonoids shows a good correlation with a regression equation of log IC50 = 0.8069 ΔGbind + 9.4456(r = 0.9226; P50 values of the quercetin derivatives were calculated. The predicted IC50 values of quercetin-3-O-acetate; 6-chloroquercetin,3-O-acetate; 6,8-dibromoquercetin; 6,8-dichloroquercetin-3-O-acetate and 6,8-dibromoquercetin-3-O-acetate are lower than thats of quercetin. These results show that only substitutions at certain position on quercetin with acetyl group, chlorine and bromine atoms increase the inhibitory activity of quercetin against COX-2.


Keywords


Docking; flavonoids; quercetin derivatives; cyclooxygenase-2; anti-inflammatory

Full Text:

Full Text PDF


References

[1] Oda, A., Okayasu, M., Kamiyama, Y., Yoshida, T., Takahashi, O., and Matsuzaki, H., 2007, Bull. Chem. Soc. Jpn., 80, 10, 1920-1925.

[2] Joy, S., Nair, P.S., Hariharan, R., and Pillai, M.R., 2006, In Silico Biology, 6, 53.

[3] Soberman, R.J. and Christmas, P., 2003, J. Clin. Invest., 111,1107-1113.

[4] Takano-Ishikawa, Y., Goto, M., And Yamaki, K., 2006, Phytomedicine, 13, 5, 310-317.

[5] Chen, Y.C., Shen, S.C., Lee, W.R., Hou, W.C., Yang, L.L., and Lee, T.J., 2001, J. Cell. Biochem., 82, 537-548.

[6] Morikawa, K., Nonaka, M., Narahara, M, Torii, I., Kawaguchi, K., Yoshikawa, T., Kumazawa, Y., and Morikawa, S., 2003, Life Sci., 26, 6, 709-21.

[7] Wu, C.M., Wu, S.C., W., Chung, W.J., Lin. H.C., Chen, K.T., Chen, Y.C., Hsu, M.F., Yang, J.M., Wang, J.P., and Lin, C.N., 2007, Int. J. Mol. Sci., 8, 830-841.

[8] Kiefer, J.R., Pawlitz, J.L., Moreland, K.T., Stegeman, R.A., Hood, W.F., Gierse, J.K., Stevens, A.M., Goodwin, D.C., Rowlinson, S.W., Marnett, L.J., Stallings, W.C., and Kurumbail, R.G., 2000, Nature¸ 405, 97-101.

[9] Zheng, M., Zhang, Z., Zhu, W., Liu, H., Luo, X., Chen, K. and Jiang, H., 2006, Bioorg. Med. Chem., 14, 3428-3437.

[10] Ji, H.F. and Zhang, 2006, J. Mol. Struct., THEOCHEM, 767, 3–9.

[11] Anonymous, 2004, ArgusLab 4.0.1., Tutorial and FAQs, Mark Thompson and Plannaria Software LLC.

[12] Akaho, E., Fujikawa, C., Runion, H.I., Hill, C.R., and Nakano, H., 1999, DOCK : Applied Structure-Based Drug Design, University of California, San Francisco.

[13] Morris, G.M., and Lim-Wilby, M., “Molecular Docking” in Methods in Molecular Biology, vol. 443, Molecular Modeling of Proteins. Eds. Andreas Kukol., Humana Press, New Jersey, 2001,365-83.

[14] Akaho, E., Morris, G., Goodsell, D., Wong, D., and Olson A., 2001, J. Chem. Software, 7 (3), 416-231.



DOI: https://doi.org/10.22146/ijc.21545

Article Metrics

Abstract views : 3295 | views : 10131


Copyright (c) 2010 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 

Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web Analytics View The Statistics of Indones. J. Chem.