Browse > Article
http://dx.doi.org/10.3839/jabc.2011.010

The Roles of Hydroxyl Substituents in Tyrosinase Inhibitory Activation of Flavone Analogues  

Park, Joon-Ho (Department of Biology, Queen's University)
Sung, Nack-Do (Department of Applied Biology and Chemistry, College of Agriculture and Life Science, Chungnam National University)
Publication Information
Journal of Applied Biological Chemistry / v.54, no.1, 2011 , pp. 56-62 More about this Journal
Abstract
Molecular docking of polyhydroxy substituted flavone analogues (1-25) as substrate molecules to the active site of tyrosinase (PDB ID: Deoxy-form (2ZMX) & Oxy-form (1WX2)) and Free-Wilson analysis were studied to understand the roles of hydroxyl substituents ($R_1-R_9$) in substrate molecules for the tyrosinase inhibitory activation. It is founded from Free-Wilson analysis that the $R_1$=hydroxyl among $R_1-R_9$ substituents had the strongest influence on the tyrosinase inhibitory activity. H-bonds between the hydroxyl substituents of substrate molecules and amino acid residues in the active site of tyrosinase were contributed to make a stable substrate-receptor complex compound. Particularly, it is proposed from the findings that the noncompetitive inhibitory activation would take place via H-bonding between peroxide oxygen (Per404) atom in the active site of tyrosinase and the hydroxyl substituents in substrate molecule.
Keywords
flavone analogues; H-bonds; molecular docking; noncompetitive inhibitory activation; tyrosinase inhibition;
Citations & Related Records
Times Cited By KSCI : 5  (Citation Analysis)
연도 인용수 순위
1 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.   DOI   ScienceOn
2 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.
3 Natsch A, Emter R, and Ellis G (2009) Filling the concept with data: Integrating data from different in-vitro and in-silico assays on skin sensitizers to explore the battery approach for animal-free skin sensitization testing. Toxicol Sci 107, 106-121.   DOI
4 Neeley E, Fritch G, Fulle A, Wolfe J, Wright J, and Flurkey W (2009) Variations in IC50 values with purity of mushroom tyrosinase. Int J Mol Sci 10, 3811-3823.   DOI   ScienceOn
5 Jain AN (2003) Surflex: fully automatic flexible molecular docking using molecular similarity-based search engine. J Med Chem. 46, 499-511.   DOI   ScienceOn
6 Kubinyi H (1993) In QASR: Hansch Analysis and Related Approaches. Applications of Free Wilson Analysis and Related Models. Mannhold R, Larsen K, and Timmerman H (eds), Methods and Principles in Medicinal Chemistry 1, 139-147. VCH Verlagsgeslschaft mbH, Weinheim, Germany.
7 Khan MTH (2007) Molecular design of tyrosinase inhibitors: A critical review of promising novel inhibitors from synthetic origins. Pure Appl Chem 79, 2277-2295.   DOI   ScienceOn
8 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.   DOI   ScienceOn
9 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.   DOI   ScienceOn
10 Lam KW, Syahida A, Haq ZU, Rahman MBA, and Lajis NH (2010) Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors. Bioorg Med Chem Lett 20, 3755-3759.   DOI   ScienceOn
11 Chang TS (2009) An updated review of tyrosinase inhibitors. Int J Mol Sci 10, 2440-2475.   DOI   ScienceOn
12 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.   DOI   ScienceOn
13 Etter MC (1990) Encoding and decoding hydrogen-bond patterns of organic compounds. Acc Chem Res 23, 120-126.   DOI
14 Choi MY, Song HS, Hur HS, and Sim SS (2008) Whitening activity of luteolin related to the inhibition of cAMP pathway in a-MSHstimulated B16 melanoma cells. Arch Pharm Res 31, 1166-1171.   DOI   ScienceOn
15 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.   DOI
16 Deeth RJ and Diedrich C (2010) Structural and mechanistic insights into the oxy form of tyrosinase from molecular dynamics simulations. J Biol Inorg Chem 5, 117-129.
17 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.   DOI   ScienceOn
18 Itoh K, Hirata N, Masuda M, Naruto S, Murato K, Wakabayashi K, and Matsuda H (2009) Inhibitory effects of Citrus hassaku extract and its flavanone glycosides on melanogenesis. Biol Pharm Bull 32, 410-415.   DOI   ScienceOn
19 Arung ET, Shimizu K, and Kondo R (2006) Inhibitory effect of artocarpanone from Artocarpus heterophyllus on melanin biosynthesis. Biol Pharm Bull 29, 1966-1969.   DOI   ScienceOn
20 Andersen QM and Markham KR (2006) Flavonoids: Chemistry, Biochemistry and Applications. CRC Press. Taylor & Francis Group, Boca Raton, FL.
21 Zheng ZP, Cheng KW, To JT, and Li H (2008) Isolation of tyrosinase inhibitors from Artocarpus heterophyllus and use of its extract as antibrowning agent. Mol Nutr Food Res 52, 1530-1538.   DOI   ScienceOn
22 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-dihydroxylbenzoate and N-alkyl-3,4-dihydroxy benzamide derivatives. J Soc Cosmet Scientists Korea 30, 491-497.
23 Tokiwa Y, Kitagawa M, and Raku T (2007) Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on mushroom tyrosinase. Biotechnol Lett 29, 481-486.   DOI   ScienceOn
24 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.   DOI   ScienceOn
25 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.
26 Zhang C, Lu Y, Tao L, Tao X, Su X, and Wei D (2007) Tyrosinase inhibitory effects and inhibition mechanism of nobiletin and hesperidin from citrus peel crude extracts. J Enzyme Inhib Med Chem 22, 83-90.   DOI   ScienceOn
27 Park J and Sung ND (2010) 3D-QSARs analysis for tyrosinase inhibitory activity of 2-phenyl-1,4-benzopyrone (Flavones) analogues and molecular docking. 53, 225-231.   DOI   ScienceOn
28 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.   DOI   ScienceOn
29 Rendon MI and Gaviria JI (2005) Review of skin-lightening agents. Dermatol Surg 31, 886-889.
30 Ryu YB, Ha TJ, Curtis-Long MJ, Ryu HW, Gal SW, and Park KH (2008) Inhibitory effects on mushroom tyrosinase by flavones from the stem barks of Morus lhou (S.) Koidz. J Enzyme Inhib Med Chem 23, 922-930.   DOI   ScienceOn
31 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.
32 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.
33 Solano F, Briganti S, Picardo M, and Ghanem G (2006) Hypopigmenting agents: An update review on biological, chemical and clinical aspects. Pigment Cell Res 19, 550-571.   DOI   ScienceOn
34 Sun J, Cai S, Yan WN, and Mei H (2010) Docking and 3D-QSAR studies of influenza neuraminidase inhibitors using threedimensional holographic vector of atomic interaction field analysis. European J Med Chem 45, 1008-1014.   DOI   ScienceOn