Tyrosinase Inhibition by 4-Substituted Benzaldehydes with Electron-Withdrawing Groups

Appl Biochem Biotechnol. 2020 Aug;191(4):1711-1716. doi: 10.1007/s12010-020-03295-w. Epub 2020 Mar 24.

Abstract

The oxidation of 4-t-butylcatechol catalyzed by mushroom tyrosinase was inhibited by 4-bromobenzaldehyde, 4-chlorobenzaldehyde, 4-fluorobenzaldehyde, 4-cyanobenzaldehyde, and 4-nitrobenzaldehyde with 50% inhibitory concentrations of 114 μM, 175 μM, 387 μM, 822 μM, and 1846 μM, respectively. The inhibition kinetics were analyzed by Dixon plots, which indicated that a series of 4-hallogenated benzaldehydes acted as partial noncompetitive inhibitors in the same manner as benzaldehyde. Although β values were decreased with an increase of the tyrosinase inhibitory activity, full inhibition could not be observed. In contrast, 4-cyanobenzaldehyde and 4-nitrobenzaldehyde acted as mixed and noncompetitive inhibitors, respectively. Full inhibition was particularly represented by 4-nitrobenzaldehyde. According to a previous report, 4-alkylbenzaldehyde and 4-alkoxybenzaldehyde with a bulky substituent acted as full inhibitors. Those results suggested that the steric factor at the 4-position triggered the alternation between partial or full tyrosinase inhibition irrespective of electronic or hydrophobic effects.

Keywords: 4-Substituted benzaldehydes; Dixon plot; Full inhibitor; Noncompetitive inhibition; Partial inhibitor; Tyrosinase.

MeSH terms

  • Agaricales / chemistry
  • Benzaldehydes / chemistry*
  • Benzaldehydes / pharmacology
  • Catalysis
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Electrons
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Kinetics
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / chemistry
  • Oxidation-Reduction

Substances

  • Benzaldehydes
  • Enzyme Inhibitors
  • 4-nitrobenzaldehyde
  • 4-cyanobenzaldehyde
  • 4-chlorobenzaldehyde
  • Monophenol Monooxygenase
  • 4-fluorobenzaldehyde
  • benzaldehyde