The Guanidine Pseudoalkaloids 10-Methoxy-Leonurine and Leonurine Act as Competitive Inhibitors of Tyrosinase

Biomolecules. 2020 Jan 23;10(2):174. doi: 10.3390/biom10020174.

Abstract

: Tyrosinase plays a key role in the production of melanin. A variety of industrial fields have shown interest in the development of tyrosinase inhibitors from plants. In this study, compounds 1-5 derived from Leonurusjaponicas were evaluated to determine their ability to inhibit tyrosinase. Of these, 10-methoxy-leonurine (1) and leonurine (2) exhibited IC50 values of 7.4 ± 0.4 and 12.4 ± 0.8 μM, respectively, and acted as competitive inhibitors of tyrosinase, with Ki values in the micromolar range. In silico modeling revealed a guanidine group located in the inner cavity and a benzene ring docked within the active site of these compounds. These guanidine pseudoalkaloids show potential not only as tyrosinase inhibitors but also as lead compounds in new scaffolds for the development of novel inhibitors.

Keywords: Leonurus japonicas; competitive inhibitor; guanidine pseudoalkaloid; lead compound; tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Binding, Competitive
  • Catalytic Domain
  • Cluster Analysis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / chemistry
  • Guanidine / chemistry*
  • Inhibitory Concentration 50
  • Kinetics
  • Melanins / chemistry
  • Molecular Docking Simulation
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Enzyme Inhibitors
  • Melanins
  • leonurine
  • Gallic Acid
  • Monophenol Monooxygenase
  • Guanidine