1.
2.
Solomon EI, Sundaram UM, Machonkin TE. Chem Rev. 1996,
96(7):2563-606.
Sánchez-Ferrer A, Rodríguez-López JN, García-Cánovas F, García-
Carmona F. Biochim Biophys Acta (BBA)/Protein Struct Mol. 1995,
1247(1):1-1.
41. Ubeid AA, Zhao L, Wang Y, Hantash BM. J Invest Dermatol. 2009,
129(9):2242-9.
42. Chen QX, Ke LN, Song KK, Huang H, Liu XD. The Prot J. 2004,
23(2):135-41.
43. Shiino M, Watanabe Y, Umezawa K. Bioorg Chem. 2001, 9(5):1233-
40.
44. Mosmann T. J Immu Meth. 1983, 65(1-2):55-63.
45. Hah YS, Cho HY, Lim TY, Park DH, Kim HM, Yoon J, Kim JG, Kim
CY, Yoon TJ. Annals of Dermatol. 2012, 24(2):151-7.
46. Hearing VJ, Jimenez M. Pigment Cell Research. 1989, (2):75-85.
47. Pintus F, Matos MJ, Vilar S, Hripcsak G, Varela C, Uriarte E, Santana
L, Borges F, Medda R, Di Petrillo A, Era B. Bioorg Chem. 2017,
25(5):1687-95.
3.
4.
van Holde KE, Miller KI, Decker H.
276(19):15563-6.
J Biol Chem. 2001,
Slominski A, Zmijewski MA, Pawelek J. Pigment Cell Melanoma Res.
2012, 25(1):14-27.
5.
6.
7.
8.
9.
Slominski A, Costantino R. Experi. 1991, 47(7):721-4.
Slominski A, Costantino R. Life Sci. 1991, 48(21):2075-9.
Slominski A, Paus R. J Theoretical Bio. 1990, 143(1):123-38.
Prota G. Melanins and melanogenesis. Acad Press; 2012.
Prota G. In Fortschritte der Chemie Organis Naturstoffe/Progress in the
Chemistry of Organic Natural Products 1995, 93-148. Springer, Vienna.
10. Kadekaro AL, Kanto H, Kavanagh R, ABDEL‐MALEK ZA. Annals of
the New York Acad Sci. 2003, 994(1):359-65.
O
O
O
O
11. Petit L, Pierard GE. Int J Cosmet Sci. 2003, 25(4):169-81.
12. Riley PA. Pigment Cell Res. 2003, 16(5):548-52.
13. Uong A, Zon LI. J Cell Physiol. 2010, 222(1):38-41.
14. Yamaguchi Y, Hearing VJ. Cold Spring Harb Perspect Med. 2014,
4(5):a017046.
O
OH
Tyrosinase Inhibitor IC50= 5.7 uM
15. Chen WC, Tseng TS, Hsiao NW, Lin YL, Wen ZH, Tsai CC, Lee YC,
Lin HH, Tsai KC. Sci Rep. 2015, 5:7995.
16. Jimbow K, Obata H, Pathak MA, Fitzpatrick TB, J Invest Dermatol.
1974, 62: 436-49.
17. T. Pillaiyar, V. Namasivayam, M. Manickam, S.H. Jung, J Med Chem.
2018, 17, 7395e7418.
18. Ishioka W, Oonuki S, Iwadate T, Nihei KI. Bioorganic Med Chem Lett.
2019, 29(2):313-6.
19. Ullah S, Park Y, Ikram M, Lee S, Park C, Kang D, Yang J, Akter J,
Yoon S, Chun P, Moon HR. Bioorg Chem. 2018, 26(21):5672-81.
20. Scozzafava A, Passaponti M, Supuran CT, Gülçin İ. J Enzyme Inhib
Med Chem. 2015, 30(4):586-91.
Melanin inhibit
21. Galzigna L, Licit L, De GP, Bonora GM, Signor A. Farmaco (Societa
Chimi Italia: 1989). 1993, 48(1):95-103.
22. Chou TH, Ding HY, Hung WJ, Liang CH. Exper Dermatol. 2010,
19(8):742-50.
23. Makni M, Chtourou Y, Fetoui H, Garoui EM, Boudawara T, Zeghal N.
Eur J Pharmacol. 2011, 668(1-2):133-9.
24. Prince, P. S. M., Raja kumar, S. & Dhanasekar, K. Eur J Pharmacol.
2011, 668, 233-240.
25. Tai A, Sawano T, Yazama F, Ito H. Biochim Biophys Acta (BBA)-Gen
Sub. 2011, 1810(2):170-7.
26. Moridani MY, Cheon SS, Khan S, O'Brien PJ. Chem Biol Interact.
2003,142(3):317-33.
48.
Molecular docking (PDB ID 2Y9X)
27. You A, Zhou J, Song S, Zhu G, Song H, Yi W. Bioorg Chem.2015,
23(5):924-31.
28. Menezes JC, Kamat SP, Cavaleiro JA, Gaspar A, Garrido J, Borges F.
Eur J Med Chem. 2011, 46(2):773-7.
29. Miliovsky M, Svinyarov I, Mitrev Y, Evstatieva Y, Nikolova D,
Chochkova M, Bogdanov MG. Eur J Med Chem. 2013, 66:185-92.
30. Shi Y, Chen QX, Wang Q, Song KK, Qiu L. Food Chem. 2005,
92(4):707-12.
Kinetic analysis of th
49.
Table 1. Tyrosinase inhibitory activity, substitution pattern,
kinetics and % yield of compounds (4a-e) and (6a-c)
31. Ashraf Z, Rafiq M, Nadeem H, Hassan M, Afzal S, Waseem M, Afzal
K, Latip J. PLoS One. 2017, 12(5):e0178069.
32. Ashraf Z, Rafiq M, Seo SY, Kwon KS, Babar MM. Eur J Med Chem.
Mushroom tyrosinase
2015, 98:203-11.
Compounds
R1
R2
Ki(µM)
Yi
IC50 (µM)
33. Ashraf Z, Rafiq M, Seo SY, Babar MM. Bioorg Chem.2015.
23(17):5870-80.
4a
4b
4c
4d
4e
6a
314.5 ± 12.6
337.7 ± 17.2
298.7 ± 15.6
23.8 ± 3.7
192.7 ± 11.6
39.4 ± 4.5
3-OH
4-OH
3,4-di-OH
2,4-di-OH
3,5-di-OH
n.d.*
-
-
130
n.d.*
-
34. Ashraf Z, Rafiq M, Seo SY, Babar MM, Zaidi NU. J Enzyme Inhib Med
Chem.2015, 30(6):874-83.
35. Parvez S, Kang M, Chung HS, Bae H. Phyther Res. 2007, 21(9):805-16.
36. Abbas Q, Ashraf Z, Hassan M, Nadeem H, Latif M, Afzal S, Seo SY.
Drug Des Devel Ther.2017; 11: 2029.
37. Baell JB, Nissink JW. Seven Year Itch: ACS Chem Bio. 2017, 13(1):36-
-H
44.
6b
6c
172.8 ± 8.8
5.7 ± 0.3
16.7 ± 2.8
38. Seo WD, Ryu YB, Curtis-Long MJ, Lee CW, Ryu HW, Jang KC, Park.
2-OH
4-OH
-
Eur J Med Chem. 2010, 45(5).
11
n.d.*
39. Loizzo, M. R.; Tundis, R.; Menichini, F. Compr. Rev. Food Sci. Food
Kojic Acid
Saf. 2012, 11, 378-398.
*n.d.= not determined
40. Parvez S, Kang M, Chung HS, Bae H. Phyther Res. 2008;22(4):544–
549.
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