30
1 Melanin Chemistry
96. A. Napolitano, P.D. Donato, G. Prota, New regulatory mechanisms in the biosynthesis of
pheomelanins: rearrangement versus redox exchange reaction routes of a transient 2H-1,4benzothiazine-o-quinonimine intermediate. Biochim. Biophys. Acta 1475, 47–54 (2000)
97. A. Napolitano, C. Costantini, O. Crescenzi, G. Prota, Characterisation of 1,4-benzothiazine
intermediates in the oxidative conversion of 5-S-cysteinyldopa to pheomelanin. Tetrahedron
Lett. 35, 6365–6368 (1994)
98. A. Napolitano, M.D. Lucia, L. Panzella, M. d’Ischia, The “benzothiazine” chromophore of
pheomelanins: a reassessment. Photochem. Photobiol. 84, 593–599 (2008)
99. K. Wakamatsu, K. Ohtara, S. Ito, Chemical analysis of late stages of pheomelanogenesis:
conversion of dihydrobenzothiazine to a benzothiazole structure. Pigment Cell Melanoma
Res. 22, 474–486 (2009)
100. E.J. Land, C.A. Ramsden, P.A. Riley, Pulse radiolysis studies of ortho-quinone chemistry
relevant to melanogenesis. J. Photochem. Photobiol. B Biol. 64, 123–135 (2001)
101. A. Napolitano, P.D. Donato, G. Prota, Zinc-catalyzed oxidation of 5-S-cysteinyldopa
to 2,2’-bi(2H-1,4-benzothiazine): tracing the biosynthetic pathway of trichochromes the
characteristic pigments of red hair. J. Org. Chem. 66, 6958–6966 (2001)
102. P.D. Donato, A. Napolitano, G. Prota, Metal ions as potential regulatory factors in the biosynthesis of red hair pigments: a new benzothiazole intermediate in the iron or copper assisted
oxidation of 5-S-cysteinyldopa. Biochim. Biophys. Acta 1571, 157–166 (2002)
103. A. Biesemeier, U. Schraermeyer, O. Eibl, Chemical composition of melanosomes lipofuscin
and melanolipofuscin granules of human RPE tissues. Exp. Eye Res. 93, 29–39 (2011)
104. Y. Liu, L. Hong, K. Wakamatsu, S. Ito, B. Adhyaru, C.Y. Cheng, C.R. Bowers, J.D. Simon,
Comparison of structural and chemical properties of black and red human hair melanosomes.
Photochem. Photobiol. 81, 135–144 (2005)
105. K. Thörneby-Andersson, O. Sterner, C. Hansson, Tyrosinase-mediated formation of a reactive
quinone from the depigmenting agents 4-tert-butylphenol and 4-tert-butylcatechol. Pigment
Cell Res. 13, 33–38 (2000)
106. P. Manini, A. Napolitano, W. Westerhof, P.A. Riley, M. d’Ischia, A reactive ortho-quinone
generated by tyrosinase-catalyzed oxidation of the skin depigmentating agent monobenzone: self-coupling and thiol-conjugation reactions and possible implications for melanocyte
toxicity. Chem. Res. Toxicol. 22, 1398–1405 (2009)
107. K. Hasegawa, S. Ito, S. Inoue, K. Wakamatsu, H. Ozeki, I. Ishiguro, Dihydro-1,4benzothiazine-6,7-dione, the ultimate toxic metabolite of 4-S-cysteaminylphenol and 4-Scysteaminylcatechol. Biochem. Pharmacol. 53, 1435–1444 (1997)
108. S. Ito, M. Ojika, T. Yamashita, K. Wakamatsu, Tyrosinase-catalyzed oxidation of rhododendrol
produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: implications
for melanocyte toxicity. Pigment Cell Melanoma Res. 27, 744–753 (2014)
109. S. Ito, W. Gerwat, L. Kolbe, T. Yamashita, M. Ojika, K. Wakamatsu, Human tyrosinase is able
to oxidize both enantiomers of rhododendrol. Pigment Cell Melanoma Res. 27, 1149–1153
(2014)
110. V. Hariharan, J. Klarquist, M.J. Reust, A. Koshoffer, M.D. McKee, R.E. Boissy, I.C. Le Poole,
Monobenzyl ether of hydroquinone and 4-tertiary butyl phenol activate markedly different
physiological responses in melanocytes: relevance to skin depigmentation. J. Invest. Dermatol.
130, 211–220 (2010)
111. S. Toosi, S.J. Orlow, P. Manga, Vitiligo-inducing phenols activate the unfolded protein
response in melanocytes resulting in upregulation of IL6 and IL8. J. Invest. Dermatol. 132,
2601–2609 (2012)
112. F. Yang, R. Sarangarajan, I.C. Le Poole, E.E. Medrano, R.E. Boissy, The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase
activity. J. Invest. Dermatol. 114, 157–164 (2000)
113. J.G. van den Boorn, D.I. Picavet, P.F. van Swieten, H.A. van Veen, D. Konijnenberg, P.A. van
Veelen, T. van Capel, E.C. de Jong, E.A. Reits, J.W. Drijfhout, J.D. Bos, C.J.M. Melief, R.M.
Luiten, Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward
pigmented cells by tyrosinase haptenation and melanosome autophagy. J. Invest. Dermatol.
131, 1240–1251 (2011)
1 Melanin Chemistry
96. A. Napolitano, P.D. Donato, G. Prota, New regulatory mechanisms in the biosynthesis of
pheomelanins: rearrangement versus redox exchange reaction routes of a transient 2H-1,4benzothiazine-o-quinonimine intermediate. Biochim. Biophys. Acta 1475, 47–54 (2000)
97. A. Napolitano, C. Costantini, O. Crescenzi, G. Prota, Characterisation of 1,4-benzothiazine
intermediates in the oxidative conversion of 5-S-cysteinyldopa to pheomelanin. Tetrahedron
Lett. 35, 6365–6368 (1994)
98. A. Napolitano, M.D. Lucia, L. Panzella, M. d’Ischia, The “benzothiazine” chromophore of
pheomelanins: a reassessment. Photochem. Photobiol. 84, 593–599 (2008)
99. K. Wakamatsu, K. Ohtara, S. Ito, Chemical analysis of late stages of pheomelanogenesis:
conversion of dihydrobenzothiazine to a benzothiazole structure. Pigment Cell Melanoma
Res. 22, 474–486 (2009)
100. E.J. Land, C.A. Ramsden, P.A. Riley, Pulse radiolysis studies of ortho-quinone chemistry
relevant to melanogenesis. J. Photochem. Photobiol. B Biol. 64, 123–135 (2001)
101. A. Napolitano, P.D. Donato, G. Prota, Zinc-catalyzed oxidation of 5-S-cysteinyldopa
to 2,2’-bi(2H-1,4-benzothiazine): tracing the biosynthetic pathway of trichochromes the
characteristic pigments of red hair. J. Org. Chem. 66, 6958–6966 (2001)
102. P.D. Donato, A. Napolitano, G. Prota, Metal ions as potential regulatory factors in the biosynthesis of red hair pigments: a new benzothiazole intermediate in the iron or copper assisted
oxidation of 5-S-cysteinyldopa. Biochim. Biophys. Acta 1571, 157–166 (2002)
103. A. Biesemeier, U. Schraermeyer, O. Eibl, Chemical composition of melanosomes lipofuscin
and melanolipofuscin granules of human RPE tissues. Exp. Eye Res. 93, 29–39 (2011)
104. Y. Liu, L. Hong, K. Wakamatsu, S. Ito, B. Adhyaru, C.Y. Cheng, C.R. Bowers, J.D. Simon,
Comparison of structural and chemical properties of black and red human hair melanosomes.
Photochem. Photobiol. 81, 135–144 (2005)
105. K. Thörneby-Andersson, O. Sterner, C. Hansson, Tyrosinase-mediated formation of a reactive
quinone from the depigmenting agents 4-tert-butylphenol and 4-tert-butylcatechol. Pigment
Cell Res. 13, 33–38 (2000)
106. P. Manini, A. Napolitano, W. Westerhof, P.A. Riley, M. d’Ischia, A reactive ortho-quinone
generated by tyrosinase-catalyzed oxidation of the skin depigmentating agent monobenzone: self-coupling and thiol-conjugation reactions and possible implications for melanocyte
toxicity. Chem. Res. Toxicol. 22, 1398–1405 (2009)
107. K. Hasegawa, S. Ito, S. Inoue, K. Wakamatsu, H. Ozeki, I. Ishiguro, Dihydro-1,4benzothiazine-6,7-dione, the ultimate toxic metabolite of 4-S-cysteaminylphenol and 4-Scysteaminylcatechol. Biochem. Pharmacol. 53, 1435–1444 (1997)
108. S. Ito, M. Ojika, T. Yamashita, K. Wakamatsu, Tyrosinase-catalyzed oxidation of rhododendrol
produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: implications
for melanocyte toxicity. Pigment Cell Melanoma Res. 27, 744–753 (2014)
109. S. Ito, W. Gerwat, L. Kolbe, T. Yamashita, M. Ojika, K. Wakamatsu, Human tyrosinase is able
to oxidize both enantiomers of rhododendrol. Pigment Cell Melanoma Res. 27, 1149–1153
(2014)
110. V. Hariharan, J. Klarquist, M.J. Reust, A. Koshoffer, M.D. McKee, R.E. Boissy, I.C. Le Poole,
Monobenzyl ether of hydroquinone and 4-tertiary butyl phenol activate markedly different
physiological responses in melanocytes: relevance to skin depigmentation. J. Invest. Dermatol.
130, 211–220 (2010)
111. S. Toosi, S.J. Orlow, P. Manga, Vitiligo-inducing phenols activate the unfolded protein
response in melanocytes resulting in upregulation of IL6 and IL8. J. Invest. Dermatol. 132,
2601–2609 (2012)
112. F. Yang, R. Sarangarajan, I.C. Le Poole, E.E. Medrano, R.E. Boissy, The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase
activity. J. Invest. Dermatol. 114, 157–164 (2000)
113. J.G. van den Boorn, D.I. Picavet, P.F. van Swieten, H.A. van Veen, D. Konijnenberg, P.A. van
Veelen, T. van Capel, E.C. de Jong, E.A. Reits, J.W. Drijfhout, J.D. Bos, C.J.M. Melief, R.M.
Luiten, Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward
pigmented cells by tyrosinase haptenation and melanosome autophagy. J. Invest. Dermatol.
131, 1240–1251 (2011)