title: A convenient screening method to differentiate phenolic skin whitening tyrosinase inhibitors from leukoderma-inducing phenols.
abstract: BACKGROUND
  Tyrosinase is able to oxidize a great number of phenols and catechols to form ortho-quinones. Ortho-quinones are highly reactive compounds that exert cytotoxicity through binding with thiol enzymes and the production of reactive oxygen species. Certain phenolic (and catecholic) compounds are known to induce contact/occupational leukoderma through activation to ortho-quinones.
  
  
  OBJECTIVE
  We report a convenient screening method to follow the oxidation of those leukoderma-inducing phenols by mushroom tyrosinase.
  
  
  METHODS
  Oxidation of phenolic compounds by mushroom tyrosinase was followed periodically by UV-vis spectrophotometry. The production of ortho-quinones were confirmed by their absorptions around 400-420 nm. HPLC analysis after reduction with NaBH4 detected the corresponding catechols.
  
  
  RESULTS
  Leukoderma-inducing phenols, rhododendrol, raspberry ketone, 4-methoxyphenol, 4-benzyloxyphenol, 4-tert-butylphenol, and 4-tert-butylcatechol, were readily oxidized by mushroom tyrosinase to form ortho-quinones. On the other hand, phenolic skin whitening tyrosinase inhibitors, ellagic acid, 4-n-butylresorcinol, potassium 4-methoxysalicylate, and 2,2'-dihydroxy-5,5'-di-n-propylbiphenyl, were not oxidized by mushroom tyrosinase, while arbutin was only slowly oxidized.
  
  
  CONCLUSIONS
  This study has provided a convenient screening method to differentiate phenolic skin whitening tyrosinase inhibitors from leukoderma-inducing phenols. A common chemical feature of the latter group of compounds is that they are readily oxidized by tyrosinase to form reactive ortho-quinone species. The present results point out the necessity that tyrosinase inhibitors should also be examined as substrates if they are phenolic compounds.
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192 Japan. Electronic address: sito@fujita-hu.ac.jp.
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192 Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
mesh_terms: D004791:Enzyme Inhibitors / Q000032:analysis*; D017496:Hypopigmentation / Q000139:chemically induced*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010636:Phenols / Q000032:analysis* / Q000378:metabolism; D011809:Quinones / Q000032:analysis*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D004791:Enzyme Inhibitors; D010636:Phenols; D011809:Quinones; D014442:Monophenol Monooxygenase
keywords: Melanocyte toxicity; Rhododendrol; Tyrosinase; Tyrosinase inhibitor; Whitening agent