Rational design, synthesis and structure-activity relationships of 4-alkoxy- and 4-acyloxy-phenylethylenethiosemicarbazone analogues as novel tyrosinase inhibitors

Bioorg Med Chem. 2015 Mar 1;23(5):924-31. doi: 10.1016/j.bmc.2015.01.024. Epub 2015 Jan 22.

Abstract

In continuing our program aimed to search for potent compounds as highly efficient tyrosinase inhibitors, here a series of novel 4-alkoxy- and 4-acyloxy-phenylethylenethiosemicarbazone analogues were designed, synthesized and their biological activities on mushroom tyrosinase were evaluated. Notably, most of compounds displayed remarkable tyrosinase inhibitory activities with IC50 value of lower than 1.0μM. Furthermore, the structure-activity relationships (SARs) were discussed and the inhibition mechanism and the inhibitory kinetics of selected compounds 7k and 8d were also investigated. Taken together, these results suggested that such compounds could serve as the promising candidates for the treatment of tyrosinase-related disorders and further development of such compounds might be of great interest.

Keywords: 4-Alkoxy- and 4-acyloxy-phenylethylenethiosemicarbazone analogues; Inhibition mechanism; Inhibitory kinetics; SARs; Tyrosinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Kinetics
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemical synthesis
  • Thiosemicarbazones / chemistry*
  • Thiosemicarbazones / pharmacology*

Substances

  • Enzyme Inhibitors
  • Thiosemicarbazones
  • Monophenol Monooxygenase