Synthesis and tyrosinase inhibitory activities of 4-oxobutanoate derivatives of carvacrol and thymol

Bioorg Med Chem Lett. 2019 Jan 1;29(1):56-58. doi: 10.1016/j.bmcl.2018.11.013. Epub 2018 Nov 8.

Abstract

Carvacrol (1) and thymol (2) were converted to their alkyl 4-oxobutanoate derivatives (7-20) in three steps, and evaluated for tyrosinase inhibitory activity. The compounds showed structure-dependent activity, with all alkyl 4-oxobutanoates, except 7 and 20, showing better inhibitory activity than the precursor 4-oxobutanoic acids (5 and 6). In general, thymol derivatives exhibited a higher percent inhibitory activity than carvacrol derivatives at 500 μM. Derivatives containing three-carbon and four-carbon alkyl groups gave the strongest activity (carvacrol derivatives 9-12, IC50 = 128.8-244.1 μM; thymol derivatives 16-19, IC50 = 102.3-191.4 μM).

Keywords: Alkyl 4-oxobutanoates; Carvacrol; Thymol; Tyrosinase inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Agaricales / enzymology
  • Cymenes
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Monoterpenes / chemical synthesis
  • Monoterpenes / chemistry
  • Monoterpenes / pharmacology*
  • Structure-Activity Relationship
  • Thymol / chemical synthesis
  • Thymol / chemistry
  • Thymol / pharmacology*

Substances

  • Cymenes
  • Enzyme Inhibitors
  • Monoterpenes
  • Thymol
  • carvacrol
  • Monophenol Monooxygenase