Synthesis and preliminary in vitro biological evaluation of 4-[(4-hydroxyphenyl)sulfanyl]but-3-en-2-one, a 4-mercaptophenol derivative designed as a novel bifunctional antimelanoma agent

J Med Chem. 2009 Aug 13;52(15):4973-6. doi: 10.1021/jm900642j.

Abstract

We report the synthesis and preliminary in vitro biological evaluations of 4-[(4-hydroxyphenyl)sulfanyl]but-3-en-2-one, a compound designed as a potential bifunctional antimelanoma agent, bearing both a tyrosinase-activatable phenolic moiety and a GSH-reactive alpha,beta-unsaturated carbonyl group. Both the E (1) and Z (2) isomers of the synthesized compound proved to be very good substrates of mushroom tyrosinase, reacted quickly with GSH at physiological pH, and showed a significant cytotoxic activity against B16F1 murine melanoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Glutathione / metabolism*
  • Hydrogen-Ion Concentration
  • Melanoma, Experimental / drug therapy*
  • Mice
  • Monophenol Monooxygenase / metabolism*
  • Oxidation-Reduction
  • Phenylbutyrates / chemical synthesis*
  • Phenylbutyrates / pharmacology
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / pharmacology

Substances

  • 4-((4-hydroxyphenyl)sulfanyl)but-3-en-2-one
  • Antineoplastic Agents
  • Phenylbutyrates
  • Sulfhydryl Compounds
  • Monophenol Monooxygenase
  • Glutathione