Synthesis and Activity on Tyrosinase of Novel Chalcone Derivatives†

doi:10.7503/cjcu20131033

Abstract

Abstract:

Ver-nohia anthelmintica L was endemic plant in Xinjiang, which was often used in the treatment of Vitiligo. It was believed that the chalcone compounds of Ver-nohia anthelmintica L played an important role in this treatment. Since it may activate tyrosinase and improve the melanin production, many chalcone compounds and derivatives were described as potential inhibitor on tyrosinase which may act as skin lightening and whitening agents. However, chalcones which showed activator effect were seldom reported. In order to search for chalcones with high activities on tyrosinase, eight novel chalcone derivatives containing benzothiazole and eight amide-derived chalcones were synthesized in this work. All the compounds were idenpngied by ¹H NMR, ¹³C NMR, IR, HRMS and evaluated their activator effect on tyrosinase by measuring the oxidation rate of L-dopa. Compared with the reference drug 8-methoxypsoralen, compounds 4d, 4h, 5d, 7b and 7d showed some activator effect on tyrosinase. Amomg them, compound 7d demonstrated more potent activity with EC₅₀=9.6 μmol/L than 8-methoxypsoralen, which EC₅₀ value was 14.8 μmol/L. Further structural modification of this novel chalcones containing benzothiazole will be required for improving the solubility of them.

Key words: Chalcone, Benzothiazole, Amide, Activity on tyrosinase

CLC Number:

O629

TrendMD:

NIU Chao, LI Gen, , Haji-Akber AISA. Synthesis and Activity on Tyrosinase of Novel Chalcone Derivatives^†[J]. Chem. J. Chinese Universities, 2014, 35(6): 1204.

Figures/Tables 4

References 33

[1]	Hu X. Y., Chen B. N., Wang L., Chen F. H., Chem. Res. Chinese Universities, 2012, 28(5), 862—865
[2]	Khan K. M., Maharvi G. M., Khan M. T. H., Shaikh A. J., Perveen S., Begum S., Choudhary M. I., Bioorg. Med. Chem., 2006, 14, 344—351
[3]	Nerya O., Musa R., Khatib S., Tamir S., Vaya J., Phytochemistry, 2004, 65, 1389—1395
[4]	Fenoll L. G., Rodriguez-Lopez J. N., Varon R., Garcia-Ruiz P. A., Garcia-Canovas F., Tudela J., Biol. Chem., 2000, 381(4), 313—320
[5]	Yao L., Li Q., Shang J., J. XinJiang Medical Univ., 2010, 33(10), 1191—1193
	(姚莉, 李茜, 尚靖.新疆医科大学学报, 2010,33(10), 1191—1193 )
[6]	Deng R. C., Zhou Y., Zhang J. G., Xu J. G., Shang J., Yu L. H., Wang D. P., Amino Acids & Biotic Resources, 2002, 24(1), 31—32
	(邓瑞春, 周勇, 章金刚, 徐建国, 尚靖, 于鲁海, 王东平.氨基酸和生物资源, 2002,24(1), 31—32)
[7]	Sun L., Shang J., Li H. J., Wu L. J., Modern Chinese Medicine, 2006, 8(11), 10—12
	(孙力, 尚靖, 李红健, 吴立军.中国现代中药, 2006,8(11), 10—12)
[8]	Liu T. H., Foreign Medical Sciences, 2004, 26(2), 103—104
	(刘铜华.国外医学中医中药分册, 2004,26(2), 103—104)
[9]	Shang J., Xu J. G., Yu L. H., Sun L., Li H. J., Application of Butin and Its Derivatives in Preparing Drugs of Pigment Metabolism Disease, CP 1778294A, 2004-11-23
	(尚靖, 徐建国, 于鲁海, 孙力, 李红健. 紫铆素及其衍生物在制备色素代谢疾病药物的用途, CP 1778294A, 2004-11-23)
[10]	Yan M., Huo S. X., Gao L., Peng X. M., Preparation and Application of Flavonoid Components in Ver-nohia Anthelmintica L, CP 102526153A, 2012-02-27
	(闫明, 霍仕霞, 高莉, 彭晓明. 驱虫斑鸠菊黄酮组分及其制备方法和用途, CP 102526153A, 2012-02-27)
[11]	Khatib S., Nerya O., Musa R., Shmuel M., Tamir S., Vaya J., Bioorg. Med. Chem., 2005, 13, 433—441
[12]	Thanigaimalai P., Lee K.C., Sharma V. K., Rao E. V., Roh E., Kim Y., Jung S. H., Bioorg. Med. Chem. Lett., 2011, 21, 1922—1925
[13]	Jun N., Gao H., Jun K., Bioorg. Med. Chem., 2007, 15, 2396—2402
[14]	Zhang X. D., Hu X., Hou A. J., Wang H. Y., Biol. Pharm. Bull., 2009, 32(1), 86—90
[15]	Nixha A. R., Arslan M., Atalay Y., Gencer N., Ergun A., Arslan O., J. Enzyme. Inhib. Med. Chem., 2013, 28(4), 808—815
[16]	Sonmez F., Sevmezler S., Atahan A., Ceylan M., Demir D., Gencer N., Arslan O., Kucukislamoglu M., Bioorg. Med. Chem. Lett., 2011, 21, 7479—7482
[17]	Rao Y. K., Fang S. H., Tzeng Y. M., Bioorg. Med. Chem., 2009, 17, 7909—7914
[18]	Bandgar B. P., Patil S. A., Korbad B. L., Nile S. H., Khobragade C. N., Eur. J. Med. Chem., 2010, 45, 2629—2633
[19]	Chtourou M., Abdelhédi R., Frikha M. H., Trabelsi M., Ultrasonics Sonochemistry, 2010, 17, 246—249
[20]	Luis F. F., Boletim da Escola de Farmacia, Universidade de Coimbra, Edicao Cienpngica, 1980, 28, 49—52
[21]	Narender T., Reddy K. P., Tetrahedron Lett., 2007, 48, 3177—3180
[22]	Dimmock J. R., Jha A., Zello G. A., Allen T. M., Santos C. L., Balzarini J., de Clercq E., Manavathu E. K., Stables J. P., Pharmazie, 2003, 58(4), 227—232
[23]	Wu J. Z., Li J. L., Cai Y. P., Pan Y., Ye F. Q., Zhang Y. L., Zhao Y. J., Yang S. L., Li X. K., Liang G., J. Med. Chem., 2011, 54, 8110—8123
[24]	Keyes R. F., Gu Y. G., Sham H. L., Novel Acetyl-coa Carboxylase(ACC) Inhibitors and Their Use in Diabetes, Obesity and Metabolic Syndrome UP 20070219258A1, 2007-09-20
[25]	Zhao J. Y., Aisa H. A., Chin. J. Org. Chem., 2012, 32, 333—337
	(赵江瑜, 阿吉艾克拜尔·艾萨. 有机化学, 2012, 32, 333—337)
[26]	Gu W. L., Ma Y. N., Wang C. L., Food Science and Technology, 2010, 35(7), 48—51
	(顾玮蕾, 马跃能, 王春丽.食品科技, 2010,35(7), 48—51)
[27]	Ye X. Z., Gong S. Z., Liao G. J., Lin J. P., Zeng J. Y., China Surfactant Detergent & Cosmetics, 2010, 40(2), 98—100
	(叶孝兆, 龚盛昭, 廖国俊, 林金沛, 曾金燕.日用化学工业, 2010,40(2), 98—100)
[28]	Pathak M. A., Fitzpatrick T. B., J. Photochem. Photobiol. B: Biol., 1992, 14(1/2), 3—22
[29]	Lener A. B., Denton C. R., Fitzpatrick T. B., J. Invest. Dermatol., 1953, 20, 299—314
[30]	Parrish J. A., Fitzpatrick T. B., Tannembaum L., Pathak M. A., N. Eng. J. Med., 1974, 291(23), 1207—1211
[31]	van Weelden H., Young E., van der Leun J. C., Br. J. Dermatol., 1980, 103(1), 1—9
[32]	Morison W. L., Photodermatol. Photoimmunol. Photomed., 2004, 20, 315—320
[33]	Hong N. J., Choi S. K., Koock S. U., Bull. Korean Chem. Soc., 1989, 10(1), 19—22

Compound	R	R'	Substrate	EC₅₀/(μmol·L^-1)
4a	H	Bz	L-Tyrosine	180.6
4b	CH₃	Bz	L-Tyrosine	39.2
4c	OCH₃	Bz	L-Tyrosine	67.3
4d	Cl	Bz	L-Tyrosine	21.1
4e	CH₃	Ac	L-Tyrosine	>286
4f	Cl	Ac	L-Tyrosine	167
4g	H	Ts	L-Tyrosine	104.3
4h	Cl	Ts	L-Tyrosine	25.8
5a	H	H	L-Tyrosine	>286
5b	CH₃	H	L-Tyrosine	87.7
5c	OCH₃	H	L-Tyrosine	123.3
5d	Cl	H	L-Tyrosine	30.6
7a	H	Bz	L-Tyrosine	141
7b	CH₃	Bz	L-Tyrosine	17.1
7c	OCH₃	Bz	L-Tyrosine	55.3
7d	Cl	Bz	L-Tyrosine	9.6
8-MOP^*			L-Tyrosine	14.8

Compound	R	R'	Substrate	EC₅₀/(μmol·L^-1)
4a	H	Bz	L-Tyrosine	180.6
4b	CH₃	Bz	L-Tyrosine	39.2
4c	OCH₃	Bz	L-Tyrosine	67.3
4d	Cl	Bz	L-Tyrosine	21.1
4e	CH₃	Ac	L-Tyrosine	>286
4f	Cl	Ac	L-Tyrosine	167
4g	H	Ts	L-Tyrosine	104.3
4h	Cl	Ts	L-Tyrosine	25.8
5a	H	H	L-Tyrosine	>286
5b	CH₃	H	L-Tyrosine	87.7
5c	OCH₃	H	L-Tyrosine	123.3
5d	Cl	H	L-Tyrosine	30.6
7a	H	Bz	L-Tyrosine	141
7b	CH₃	Bz	L-Tyrosine	17.1
7c	OCH₃	Bz	L-Tyrosine	55.3
7d	Cl	Bz	L-Tyrosine	9.6
8-MOP^*			L-Tyrosine	14.8