Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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3D-QSARs analyses for Tyrosinase Inhibitory Activity of 2-Phenyl-1,4-benzopyrone (Flavones) Analogues and Molecular Docking

2-Phenyl-1,4-benzopyrone 유도체 (Flavones)의 Tyrosinase 저해활성에 관한 3D-QSARs 분석과 분자도킹

  • Park, Joon-Ho (Department of Biology, Queen's University Kingston) ;
  • Sung, Nack-Do (Department of Applied Biology and Chemistry, College of Agriculture and Life Science, Chungnam National University)
  • 박준호 (카나다 퀸스대학교 생물학과) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학과)
  • Received : 2010.10.01
  • Accepted : 2010.12.16
  • Published : 2010.12.31
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Abstract

To understand the inhibitory activity with changing hydroxyl substituents ($R_l-R_9$) of polyhydroxy substituted 2-phenyl-l,4-benzopyrone analogues (1-25) against tyrosinase (PDB ID: oxy-form; 1WX2), molecular docking and the three dimensional quantitative structure-activity relationships (3D-QSARs: Comparative molecular field analysis (CoMFA) & Comparative molecular similarity indices analysis (CoMSIA)) were studied quantitatively. The statistically best models were CoMFA 1 and CoMSIA 1 model from the results. The optimized CoMSIA 1 model with the sensitivity of the perturbation and the prediction produced ($dq^2'/dr_{yy'}^2$=1.009 & $q^2$=0.51l) by a progressive scrambling analysis were not dependent on chance correlation. The inhibitory activities with optimized CoMSIA 1 model were dependent upon electrostatic factor (51.4%) of substrate molecules. Contour mapping the 3D-QSAR models to the active site of tyrosinase provides new insight into the interaction between tyrosinase as receptor and 2-phenyl-l,4-benzopyrone analogues as inhibitor. Therefore, the results will he able to apply to the optimization of a new potent tyrosinase inhibitors.

기질분자로서 polyhydroxy 치환된 2-phenyl-l,4-benzopyrone 유도체(Flavones)(1-25)들의 hydroxyl 치환기($R_1-R_9$)가 변화함에 따른 Tyrosinase(PDB ID: oxy-form; 1WX2)에 대한 저해활성을 이해하기 위하여 분자도킹과 3차원적인 정량적 구조활성관계 (3D-QSARs: CoMFA 및 CoMSIA)가 연구되었다. 그 결과, 통계적으로 CoMFA 1 및 CoMSIA 1 모델이 가장 양호한 3D-QSARs 모델이었다. 또한, 순차 혼합화 분석결과로부터 CoMSIA 1 모델($dq^2'/dr_{yy'}^2$=1.009 및 $q^2$=0.511)이 우연상관성에 저촉되지 않는 최적화 모텔이었으며 최적화된 CoMSIA 1 모델의 tyrosinase에 대한 저해활성은 기질분자의 정전기장(51.4%)에 의존적이었다. Tyrosinase의 반응점에 대한 3D-QSAR 모델의 등고도는 수용체로서 tyrosinase과 저해제로서 2-phenyl-l,4-benzopyrone 기질분자 사이의 새로운 상호작용 관계를 이해하는 계기가 되었다. 그러므로 이 결과들은 새로운 잠재적인 tyrosinase 저해제의 최적화에 적용될 수 있을 것이다.

Keywords

References

  1. Briganti S, Camera E, and Picardo M (2003) Chemical and instrumental approaches to treat hyperpigmentation, Pigment. Cell Res 16, 101-110. https://doi.org/10.1034/j.1600-0749.2003.00029.x
  2. Chen YR, Chiou RY, Lin TY, Huang CP, Tang WC, Chen ST and Lin SB (2009) Identification of an alkylhydroquinone from Rhus succedanea as an inhibitor of tyrosinase and melanogenesis. J Agri Food Chem 57, 2200-2205. https://doi.org/10.1021/jf802617a
  3. Chen JS, Wei CI and Marshall MR (1991) Inhibition mechanism of kojic acid on polyphenol oxidase. J Agric Food Chem 39, 1897-1901. https://doi.org/10.1021/jf00011a001
  4. Choi MY, Song HS, Hur HS and Sim SS (2008) Whitening activity of luteolin related to the inhibition of cAMP pathway in $\alpha$-MSH- stimulated B16 melanoma cells. Arch Pharm Res 31, 1166-1171. https://doi.org/10.1007/s12272-001-1284-4
  5. Chung SW, Ha YM, Kim YJ, Song S, Lee H, Suh H and Chung HY (2009) Inhibitory effect of 6-(3-hydroxyphenyl)-2-naphthol on tyrosinase activity and melanin synthesis. Arch Pharm Res 32, 289-294. https://doi.org/10.1007/s12272-009-1235-9
  6. Clark RD and Fox PC (2004) Statistical variation in progressive scrambling. J Comput-Aided Mol Design 18, 563-576. https://doi.org/10.1007/s10822-004-4077-z
  7. Cramer RD, Bunce JD and Patterson DE (1988) Crossvalidation, boostrapping and partial least squares compared with multiple regression in conventional QSAR studies. Quant Struct Act Relat 7, 18-25. https://doi.org/10.1002/qsar.19880070105
  8. Ghani U and Ullah N (2010) New potent inhibitors of tyrosinase: Novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H) thiones, and substituted hydrazides to the dicopper active site. Bioorg Med Chem 18, 4042-4048. https://doi.org/10.1016/j.bmc.2010.04.021
  9. Hill H Z, Li W, Xin P and Mitchell DL (1997) Melanin; A two eged sword? Pigment Cell Res 10, 158-161. https://doi.org/10.1111/j.1600-0749.1997.tb00478.x
  10. Kim YJ and Uyama H (2005) Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the fure. Cell Mol Life Sci 62, 1707-1723. https://doi.org/10.1007/s00018-005-5054-y
  11. Khan MTH (2007a) Molecular design of tyrosinase inhibitors: A critical review of promising novel inhibitors from synthetic origins. Pure Appl Chem 79, 2277-2295. https://doi.org/10.1351/pac200779122277
  12. Kim D, Park J, Kim J, Han C, Yoon J, Kim N, Seo J and Lee C (2006) Flavonnoids as mushroom tyrosinase inhibitors: A fluorescence quenching study. J Agric Food Chem 54, 935-941. https://doi.org/10.1021/jf0521855
  13. Klebe G, Abraham U and Mietzner T (1994) Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity, J Med Chem 37, 4130-4146. https://doi.org/10.1021/jm00050a010
  14. Lam KW, Syahida A, Haq ZU, Rahman MBA and Lajis NH (2010) Synthesis and biological activity of oxadiazole and triazolo- thiadiazole derivatives as tyrosinase inhibitors. Bioorg Med Chem Lett 20, 3755-3759. https://doi.org/10.1016/j.bmcl.2010.04.067
  15. Maeda K and Fukuda M (1991) In vitro effectiveness of several whitening cosmetic components in human melanocytes. J Soc Cosmet Chem 42, 361-368.
  16. Matoba Y, Kumagai T, Yamamoto A, Yoshitsu H and Sugiyama M (2006) Crystallographic Evidence That the Dinuclear Copper Center of Tyrosinase is Flexible during Catalysis. J Biol Chem 281, 8981-8990. https://doi.org/10.1074/jbc.M509785200
  17. Mercedes J, Soledad C, Josefa E, Juana C and Francisco GC (2000) Competitive inhibition of mushroom tyrosinase by 4-substituted benzaldehydes. J Agric Food Chem 49, 4060-4063.
  18. Neeley E, Fritch G, Fulle A, Wolfe J, Wright J and Flurkey W (2009) Variations in $IC_{50}$ values with purity of mushroom tyrosinase. Int J Mol Sci 10, 3811-3823. https://doi.org/10.3390/ijms10093811
  19. Ogunnariwo J and Hamilton-miller JMT (1975) Brown- and redpigmented pseudomonas: Differentiation between melanin and pyorubrin. J Med Microbiol 8, 199-203. https://doi.org/10.1099/00222615-8-1-199
  20. Patrick AH, Jonathan BC and John OT (2008) Molecular docking of interactions and groove-binders to nucleic acids using autodock and surflex. J Chem Inf Model 48, 1602-1615. https://doi.org/10.1021/ci800063v
  21. Parvez S, Kang MK, Chung HS, Bae HS. (2007) Naturally occurring tyrosinase inhibitors: Mechanism and applications in skin health, cosmetics and agriculture industries. Phytother Res 21, 805-816. https://doi.org/10.1002/ptr.2184
  22. Sawant R, Lanke P, Jadhav G and Bhangale L (2010) QSAR analysis of structurally similar 1,3,4-oxadiazoles as enzyme tyrosinase inhibitors. Drug Invention Today 2, 169-172.
  23. Seiberg MC and Paine MS (2000) Inhibition of melanosome transfer results in skin lightening. J Invest Dermatol 115, 162-167. https://doi.org/10.1046/j.1523-1747.2000.00035.x
  24. Soung MG, Kim JH, Kwon BM and Sung ND (2010) Synthesis and ligand based 3D-QSAR of 2,3-bis-benzylidenesuccin-aldehyde derivatives as new class potent FPTase inhibitor, and prediction of active molecules. Bull Korean Chem Soc 31, 1355-1360. https://doi.org/10.5012/bkcs.2010.31.5.1355
  25. Sung ND, Jung HS and Kim SJ (2004) Hydrolytic reactivity and holographic quantitative structure-activity relationship analyses on the melanogenesis inhibitory activities of alkyl-3,4-dihydroxyl-benzoate and N-alkyl-3,4-dihydroxybenzamide derivatives. J Soc Cosmet Scientists Korea 30, 491-497.
  26. Sung ND, Chung YH, Jang SC and Kim SJ (2007) 2-D QSAR and HQSAR on the inhibition activity of protein tyrosine phosphate 1B with oleanolic acid analogues. J Appl Biol Chem 50, 52-57.
  27. Tokiwa Y, Kitagawa M and Raku T (2007) Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on mushroom tyrosinase. Biotechnology Letters 29, 481-486. https://doi.org/10.1007/s10529-006-9267-4
  28. Tollesona WH (2005) Human melanocyte biology, toxicology, and pathology. J Environ Sci Health, Part C 23, 105-161. https://doi.org/10.1080/10590500500234970
  29. Tripos Inc (2008) Sybyl molecular modeling and QSAR software on CD-Rom, (Ver.8.1.1) Theory and manual. St Louis, Missouri.
  30. Wang HM, Chen CY, Ho ML, Chou YT, Chang HC, Lee CH, Wang CZ and Chu IM (2010) (-)-N-Formylanonaine from Michelia alba as a human tyrosinase inhibitor and antioxidant, Bioorg. Med Chem 18, 5241-5247. https://doi.org/10.1016/j.bmc.2010.05.045
  31. Wold S, Johansson E and Cocchi M (1993) PLS-partial least squares projections to latent structures. In 3D-QSAR in drug design: Theory, Methods and Applications (Kubinyi H ed.), pp. 523-550. ESCOM, Leiden.
  32. Xue CB, Luo WC, Ding Q, Liu SZ and Gao XX (2008) Quantitative structure-activity relationship studies of mushroom tyrosinase inhibitors. J Comput Aided Mol Des 22, 290-309.
  33. Yagi A, Kanbara T, Morinobu N (1987) Inhibition of mushroom tyrosinase by Aloe extract. Planta Med 53, 515-517. https://doi.org/10.1055/s-2006-962798

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