Synthesis and evaluation of anti-tyrosinase activity of phenyl benzyl ether derivatives: Effects of functional groups and their positions
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Published:
Aug 31, 2018
Keywords:
monobenzone phenyl benzyl ether analogue melanogenesis anti-tyrosinase agent whitening agent
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Abstract
Thirteen phenyl benzyl ethers were synthesized and their in vitro inhibitory activity towards tyrosinase, rate-determining enzyme in melanogenesis, was evaluated. The results showed that p-substituted phenyl benzyl ethers, especially p-chlorophenyl ones (23), exhibited significantly higher inhibition percentage to the ethers substituted at meta- and ortho-positions at 500 µM. At the same concentration, polysubstituted phenyl benzyl ethers 31 and 32 exhibited comparable inhibition percentage to kojic acid. Furthermore, p-chlorophenyl (23) and tribrominated phenyl analogues (32) were proven to have similar and even higher inhibition potency compared to kojic acid (IC50 = 106 µM) with IC50 of 55.7 and 93.8 µM, respectively. This study suggested that phenyl benzyl ethers 23 and 32 might be promising candidates for skin whitening agents for pharmacological and cosmetical products.
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Suttisintong, K., Palakhachane, S., Athipornchai, A., Pimtong, W., & Limpachayaporn, P. (2018). Synthesis and evaluation of anti-tyrosinase activity of phenyl benzyl ether derivatives: Effects of functional groups and their positions. Science, Engineering and Health Studies, 12(2), 111–123. https://doi.org/10.14456/sehs.2018.10
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Research Articles
References
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Chen, Q. X. and Kubo, I. (2002). Kinetics of mushroom tyrosinase inhibition by quercetin. Journal of Agricultural and Food Chemistry, 50(14), 4108-4112.
Chen, W. C., Tseng, T. S., Hsiao, N. W., Lin, Y. L., Wen, Z. H., Tsai, C. C., and Tsai, K. C. (2015). Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling. Scientific Reports, 5, 7995.
Chompoo, J., Upadhyay, A., Fukuta, M., and Tawata, S. (2012). Effect of Alpinia zerumbet components on antioxidant and skin diseases-related enzymes. BMC Complementary and Alternative Medicine, 12, 1-9.
Cooksey, C. J., Garratt, P. J., Land, E. J., Pavel, S., Ramsden, C. A., Riley, P. A., and Smit, N. P. (1997). Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase. Journal of Biological Chemistry, 272(42), 26226-26235.
Cram, D. J., Dicker, I. B., Lauer, M., Knobler, C. B., and Trueblood, K. N. (1984). Host-guest Complexation. 32. Spherands Composed of Cyclic Urea and Anisyl Units. Journal of the American Chemical Society, 106(23), 7150-7167.
Curto, E. V., Kwong, C., Hermersdörfer, H., Glatt, H., Santis, C., Virador, V., and Dooley, T. P. (1999). Inhibitors of mammalian melanocytetyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. Biochemical Pharmacology, 57(6), 663-672.
Dubbaka, S. R., Gadde, S., and Narreddula, V. R., (2015). Synthesis of Aryl Fluorides from Potassium Aryltrifluoroborates and Selectfluor® Mediated by Iron (III) Chloride. Synthesis, 47(06), 854-860.
Fitzpatrick, T., Arndt, K. A., El Mofty, A. M., and Pathak, M. A. (1966). Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo. Archives of Dermatology, 93(5), 589-600.
Gamache, R. F., Waldmann, C., and Murphy, J. M. (2016). Copper-mediated oxidative fluorination of aryl stannanes with fluoride. Organic Letters, 18(18), 4522-4525.
Harmon, L. E. (1964). Melanogenesis and pigmentary disturbances. Journal of the National Medical Association, 56(6), 501-504.
Hermanns, J. F., Pierard-Franchimont, C., and Pierard, G. E. (2000). Skin colour assessment in safety testing of cosmetics. An overview. International Journal of Cosmetic Science, 22(1), 67-71.
Hori, I., Nihei, K. I., and Kubo, I. (2004). Structural criteria for depigmenting mechanism of arbutin. Phytotherapy Research,18(6), 475-479.
Huang, H. and Kang, J. Y. (2017). Mitsunobu Reaction Using Basic Amines as Pronucleophiles. The Journal of Organic Chemistry, 82(13), 6604-6614.
Johnson, S. M., Connelly, S., Wilson, I. A., and Kelly, J. W. (2008). Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies. Journal of Medicinal Chemistry, 51(20), 6348-6358.
Jones, K., Hughes, J., Hong, M., Jia, Q., and Orndorff, S. (2002). Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase. Pigment Cell Research, 15(5), 335-340.
Kim, Y. J. and Uyama, H. (2005). Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cellular and Molecular Life Sciences, 62(15), 1707-1723.
Kligman, A. M. and Willis, I. (1975). A new formula for depigmenting human skin. Archives of Dermatology, 111(1), 40-48.
Kubo, I. and Kinst-Hori, I. (1999). Flavonols from saffron flower: tyrosinase inhibitory activity and inhibition mechanism. Journal of Agricultural and Food Chemistry, 47(10), 4121-4125.
Lindquist, N. G. (1973). Accumulation of drugs on melanin. Acta Radiologica: Diagnosis, 325, 1-92.
Loizzo, M. R., Tundis, R., and Menichini, F. (2012). Natural and synthetic tyrosinase inhibitors as antibrowning agents: an update. Comprehensive Reviews in Food Science and Food Safety, 11(4), 378-398.
Maeda, K. and Fukuda, M. (1991). In vitro effectiveness of several whitening cosmetic components in human melanocytes. Journal of the Society of Cosmetic Chemists, 42(2), 361-368.
Mishima, Y., Hatta, S., Ohyama, Y., and Inazu, M. (1988). Induction of melanogenesis suppression: cellular pharmacology and mode of differential action. Pigment Cell Research, 1(6), 367-374.
Morin, J., Zhao, Y., and Snieckus, V. (2013). Reductive Cleavage of Aryl O-Carbamates to Phenols by the Schwartz Reagent. Expedient Link to the Directed Ortho Metalation Strategy. Organic Letters, 15(16), 4102-4105.
Nesterov, A., Zhao, J., Minter, D., Hertel, C., Ma, W., Abeysinghe, P., and Jia, Q. (2008). 1-(2, 4-Dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl) propane, a novel tyrosinase inhibitor with strong depigmenting effects. Chemical and Pharmaceutical Bulletin, 56(9), 1292-1296.
Ohyama, Y. (1990). Melanogenesis-inhibitory effect of kojic acid and its action mechanism. Fragrance Journal, 6, 53-58.
Oozeki, H., Tajima, R., and Nihei, K. I. (2008). Molecular design of potent tyrosinase inhibitors having the bibenzyl skeleton. Bioorganic and Medicinal Chemistry Letters, 18(19), 5252-5254.
Park, K. H., Lee, J. R., Hahn, H. S., Kim, Y. H., Bae, C. D., Yang, J. M., and Hahn, M. J. (2006). Inhibitory effect of ammonium tetrathiotungstate on tyrosinase and its kinetic mechanism. Chemical and Pharmaceutical Bulletin, 54(9), 1266-1270.
Parra, J. Mercader, J. V. Agulló, C., Abad-Fuentes, A., and Abad-Somovilla, A. (2011). Concise and modular synthesis of regioisomeric haptens for the production of high-affinity and stereoselective antibodies to the strobilurin azoxystrobin. Tetrahedron, 67(3), 624-635.
Parvez, S., Kang, M., Chung, H. S., Cho, C., Hong, M. C., Shin, M. K., and Bae, H. (2006). Survey and mechanism of skin depigmenting and lightening agents. Phytotherapy Research, 20(11), 921-934.
Pilkington, L. I., Wagoner, J., Polyak, S. J., and Barker, D. (2015). Enantioselective Synthesis, Stereochemical Correction, and Biological Investigation of the Rodgersinine Family of 1, 4-Benzodioxane Neolignans. Organic Letters, 17(4), 1046-1049.
Qiu, L., Chen, Q. H., Zhuang, J. X., Zhong, X., Zhou, J. J., Guo, Y. J., and Chen, Q. X. (2009). Inhibitory effects of α-cyano-4-hydroxycinnamic acid on the activity of mushroom tyrosinase. Food Chemistry, 112(3), 609-613.
Sapkota, K., Roh, E., Lee, E., Ha, E. M., Yang, J. H., Lee, E. S., and Na, Y. (2011). Synthesis and anti-melanogenic activity of hydroxyphenyl benzyl ether analogues. Bioorganic and Medicinal Chemistry, 19(7), 2168-2175.
Schmidt, B. and Riemer, M. (2016). Microwave-Promoted Deprenylation: Prenyl Ether as a Thermolabile Phenol Protecting Group. Synthesis, 48(09), 1399-1406.
Seo, S. Y., Sharma, V. K., and Sharma, N. (2003). Mushroom tyrosinase: recent prospects. Journal of Agricultural and Food Chemistry, 51(10), 2837-2853.
Singh, A. S., Shendage, S. S., and Nagarkar, J. M. (2014). Choline Chloride Based Deep Eutectic Solvent as an Efficient Solvent for the Benzylation of Phenols. Tetrahedron Letters, 55(52), 7243-7246.
Solano, F., Briganti, S., Picardo, M., and Ghanem, G. (2006). Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Research, 19(6), 550-571.
Spritz, R. A. and Hearing, V. J. (1994). Genetic disorders of pigmentation. In Advances in Human Genetics, pp. 1-45, Springer, Boston, MA.
Taniguchi, T., Imoto, M., Takeda, M., Nakai, T., Mihara, M., Iwai, T., and Ogawa, A. (2015). Hydrolysis of Diazonium Salts Using a Two‐Phase System (CPME and Water). Heteroatom Chemistry, 26(6), 411-416.
Tokiwa, Y., Kitagawa, M., Raku, T., Yanagitani, S., and Yoshino, K. (2007). Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on melanin synthesis. Bioorganic and Medicinal Chemistry Letters, 17(11), 3105-3108.
Xiong, X., Tan, F., and Yeung, Y. Y. (2017). Zwitterionic-Salt-Catalyzed Site-Selective Monobromination of Arenes. Organic Letters, 19(16), 4243-4246.
Zhang, X., Hu, X., Hou, A., and Wang, H. (2009). Inhibitory effect of 2, 4, 2′, 4′-tetrahydroxy-3-(3-methyl-2-butenyl)-chalcone on tyrosinase activity and melanin biosynthesis. Biological and Pharmaceutical Bulletin, 32(1), 86-90.
Chen, Q. X. and Kubo, I. (2002). Kinetics of mushroom tyrosinase inhibition by quercetin. Journal of Agricultural and Food Chemistry, 50(14), 4108-4112.
Chen, W. C., Tseng, T. S., Hsiao, N. W., Lin, Y. L., Wen, Z. H., Tsai, C. C., and Tsai, K. C. (2015). Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling. Scientific Reports, 5, 7995.
Chompoo, J., Upadhyay, A., Fukuta, M., and Tawata, S. (2012). Effect of Alpinia zerumbet components on antioxidant and skin diseases-related enzymes. BMC Complementary and Alternative Medicine, 12, 1-9.
Cooksey, C. J., Garratt, P. J., Land, E. J., Pavel, S., Ramsden, C. A., Riley, P. A., and Smit, N. P. (1997). Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase. Journal of Biological Chemistry, 272(42), 26226-26235.
Cram, D. J., Dicker, I. B., Lauer, M., Knobler, C. B., and Trueblood, K. N. (1984). Host-guest Complexation. 32. Spherands Composed of Cyclic Urea and Anisyl Units. Journal of the American Chemical Society, 106(23), 7150-7167.
Curto, E. V., Kwong, C., Hermersdörfer, H., Glatt, H., Santis, C., Virador, V., and Dooley, T. P. (1999). Inhibitors of mammalian melanocytetyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. Biochemical Pharmacology, 57(6), 663-672.
Dubbaka, S. R., Gadde, S., and Narreddula, V. R., (2015). Synthesis of Aryl Fluorides from Potassium Aryltrifluoroborates and Selectfluor® Mediated by Iron (III) Chloride. Synthesis, 47(06), 854-860.
Fitzpatrick, T., Arndt, K. A., El Mofty, A. M., and Pathak, M. A. (1966). Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo. Archives of Dermatology, 93(5), 589-600.
Gamache, R. F., Waldmann, C., and Murphy, J. M. (2016). Copper-mediated oxidative fluorination of aryl stannanes with fluoride. Organic Letters, 18(18), 4522-4525.
Harmon, L. E. (1964). Melanogenesis and pigmentary disturbances. Journal of the National Medical Association, 56(6), 501-504.
Hermanns, J. F., Pierard-Franchimont, C., and Pierard, G. E. (2000). Skin colour assessment in safety testing of cosmetics. An overview. International Journal of Cosmetic Science, 22(1), 67-71.
Hori, I., Nihei, K. I., and Kubo, I. (2004). Structural criteria for depigmenting mechanism of arbutin. Phytotherapy Research,18(6), 475-479.
Huang, H. and Kang, J. Y. (2017). Mitsunobu Reaction Using Basic Amines as Pronucleophiles. The Journal of Organic Chemistry, 82(13), 6604-6614.
Johnson, S. M., Connelly, S., Wilson, I. A., and Kelly, J. W. (2008). Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies. Journal of Medicinal Chemistry, 51(20), 6348-6358.
Jones, K., Hughes, J., Hong, M., Jia, Q., and Orndorff, S. (2002). Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase. Pigment Cell Research, 15(5), 335-340.
Kim, Y. J. and Uyama, H. (2005). Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cellular and Molecular Life Sciences, 62(15), 1707-1723.
Kligman, A. M. and Willis, I. (1975). A new formula for depigmenting human skin. Archives of Dermatology, 111(1), 40-48.
Kubo, I. and Kinst-Hori, I. (1999). Flavonols from saffron flower: tyrosinase inhibitory activity and inhibition mechanism. Journal of Agricultural and Food Chemistry, 47(10), 4121-4125.
Lindquist, N. G. (1973). Accumulation of drugs on melanin. Acta Radiologica: Diagnosis, 325, 1-92.
Loizzo, M. R., Tundis, R., and Menichini, F. (2012). Natural and synthetic tyrosinase inhibitors as antibrowning agents: an update. Comprehensive Reviews in Food Science and Food Safety, 11(4), 378-398.
Maeda, K. and Fukuda, M. (1991). In vitro effectiveness of several whitening cosmetic components in human melanocytes. Journal of the Society of Cosmetic Chemists, 42(2), 361-368.
Mishima, Y., Hatta, S., Ohyama, Y., and Inazu, M. (1988). Induction of melanogenesis suppression: cellular pharmacology and mode of differential action. Pigment Cell Research, 1(6), 367-374.
Morin, J., Zhao, Y., and Snieckus, V. (2013). Reductive Cleavage of Aryl O-Carbamates to Phenols by the Schwartz Reagent. Expedient Link to the Directed Ortho Metalation Strategy. Organic Letters, 15(16), 4102-4105.
Nesterov, A., Zhao, J., Minter, D., Hertel, C., Ma, W., Abeysinghe, P., and Jia, Q. (2008). 1-(2, 4-Dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl) propane, a novel tyrosinase inhibitor with strong depigmenting effects. Chemical and Pharmaceutical Bulletin, 56(9), 1292-1296.
Ohyama, Y. (1990). Melanogenesis-inhibitory effect of kojic acid and its action mechanism. Fragrance Journal, 6, 53-58.
Oozeki, H., Tajima, R., and Nihei, K. I. (2008). Molecular design of potent tyrosinase inhibitors having the bibenzyl skeleton. Bioorganic and Medicinal Chemistry Letters, 18(19), 5252-5254.
Park, K. H., Lee, J. R., Hahn, H. S., Kim, Y. H., Bae, C. D., Yang, J. M., and Hahn, M. J. (2006). Inhibitory effect of ammonium tetrathiotungstate on tyrosinase and its kinetic mechanism. Chemical and Pharmaceutical Bulletin, 54(9), 1266-1270.
Parra, J. Mercader, J. V. Agulló, C., Abad-Fuentes, A., and Abad-Somovilla, A. (2011). Concise and modular synthesis of regioisomeric haptens for the production of high-affinity and stereoselective antibodies to the strobilurin azoxystrobin. Tetrahedron, 67(3), 624-635.
Parvez, S., Kang, M., Chung, H. S., Cho, C., Hong, M. C., Shin, M. K., and Bae, H. (2006). Survey and mechanism of skin depigmenting and lightening agents. Phytotherapy Research, 20(11), 921-934.
Pilkington, L. I., Wagoner, J., Polyak, S. J., and Barker, D. (2015). Enantioselective Synthesis, Stereochemical Correction, and Biological Investigation of the Rodgersinine Family of 1, 4-Benzodioxane Neolignans. Organic Letters, 17(4), 1046-1049.
Qiu, L., Chen, Q. H., Zhuang, J. X., Zhong, X., Zhou, J. J., Guo, Y. J., and Chen, Q. X. (2009). Inhibitory effects of α-cyano-4-hydroxycinnamic acid on the activity of mushroom tyrosinase. Food Chemistry, 112(3), 609-613.
Sapkota, K., Roh, E., Lee, E., Ha, E. M., Yang, J. H., Lee, E. S., and Na, Y. (2011). Synthesis and anti-melanogenic activity of hydroxyphenyl benzyl ether analogues. Bioorganic and Medicinal Chemistry, 19(7), 2168-2175.
Schmidt, B. and Riemer, M. (2016). Microwave-Promoted Deprenylation: Prenyl Ether as a Thermolabile Phenol Protecting Group. Synthesis, 48(09), 1399-1406.
Seo, S. Y., Sharma, V. K., and Sharma, N. (2003). Mushroom tyrosinase: recent prospects. Journal of Agricultural and Food Chemistry, 51(10), 2837-2853.
Singh, A. S., Shendage, S. S., and Nagarkar, J. M. (2014). Choline Chloride Based Deep Eutectic Solvent as an Efficient Solvent for the Benzylation of Phenols. Tetrahedron Letters, 55(52), 7243-7246.
Solano, F., Briganti, S., Picardo, M., and Ghanem, G. (2006). Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Research, 19(6), 550-571.
Spritz, R. A. and Hearing, V. J. (1994). Genetic disorders of pigmentation. In Advances in Human Genetics, pp. 1-45, Springer, Boston, MA.
Taniguchi, T., Imoto, M., Takeda, M., Nakai, T., Mihara, M., Iwai, T., and Ogawa, A. (2015). Hydrolysis of Diazonium Salts Using a Two‐Phase System (CPME and Water). Heteroatom Chemistry, 26(6), 411-416.
Tokiwa, Y., Kitagawa, M., Raku, T., Yanagitani, S., and Yoshino, K. (2007). Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on melanin synthesis. Bioorganic and Medicinal Chemistry Letters, 17(11), 3105-3108.
Xiong, X., Tan, F., and Yeung, Y. Y. (2017). Zwitterionic-Salt-Catalyzed Site-Selective Monobromination of Arenes. Organic Letters, 19(16), 4243-4246.
Zhang, X., Hu, X., Hou, A., and Wang, H. (2009). Inhibitory effect of 2, 4, 2′, 4′-tetrahydroxy-3-(3-methyl-2-butenyl)-chalcone on tyrosinase activity and melanin biosynthesis. Biological and Pharmaceutical Bulletin, 32(1), 86-90.