4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase

IUBMB Life. 2016 Aug;68(8):663-72. doi: 10.1002/iub.1528. Epub 2016 Jun 24.


4-n-Butylresorcinol (BR) is considered the most potent inhibitor of tyrosinase, which is why it is used in cosmetics as a depigmenting agent. However, this work demonstrates that BR is a substrate of this enzyme. The Em (met-tyrosinase) form is not active on BR, but Eox (oxy-tyrosinase) can act on this molecule, hydroxylating it to o-diphenol. In turn, this is oxidized to an o-quinone, which isomerizes to a red p-quinone. Thus, for tyrosinase to act on this compound, a mechanism to generate Eox in the medium is required, which can be achieved by means of hydrogen peroxide or ascorbic acid. A kinetic analysis of the proposed mechanism allows its kinetic characterization: catalytic constant kcatBR (8.49 ± 0.20 s(-1) ) and Michaelis-constant KMBR (60.26 ± 8.76 μM). These findings are compared with those for other monophenolic substrates of tyrosinase. Studies of BR docking to the Em form of the enzyme show that the hydroxyl group in C-1 position is oriented toward the copper atom A (CuA), as in it is L-tyrosine. As regards Eox , BR is oriented with the carbon in C-6 position ready to be hydroxylated. The reaction of BR originates o-quinones, which isomerize to p-quinones, which in turn, could react with thiol compounds, a finding that could have important implications for pharmacology and the cosmetic industry. © 2016 IUBMB Life, 68(8):663-672, 2016.

Keywords: 4-n-butylresorcinol (BR); alternative substrate; inhibitor; kinetic analysis; tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Copper / chemistry
  • Cosmetics*
  • Humans
  • Kinetics
  • Molecular Docking Simulation
  • Monophenol Monooxygenase / chemistry*
  • Monophenol Monooxygenase / metabolism
  • Resorcinols / chemistry*
  • Resorcinols / metabolism
  • Skin Lightening Preparations / chemistry*
  • Skin Lightening Preparations / metabolism
  • Substrate Specificity


  • 4-n-butylresorcinol
  • Cosmetics
  • Resorcinols
  • Skin Lightening Preparations
  • Copper
  • Monophenol Monooxygenase