Discovery of benzylidenebenzofuran-3(2H)-one (aurones) as inhibitors of tyrosinase derived from human melanocytes.

Abstract

Tyrosinase is a copper-dependent enzyme which converts l- tyrosine to dopaquinone and is involved in different biological processes such as melanogenesis and skin hyperpigmentation. The purpose of this study was to investigate naturally occurring aurones (Z-benzylidenebenzofuran-3(2H)-one) and analogues as human tyrosinase inhibitors. Several aurones bearing hydroxyl groups on A-ring and different substituents on B-ring were synthesized and evaluated as inhibitors of human melanocyte-tyrosinase by an assay which measures tyrosinase-catalyzed l-Dopa oxidation. We found that unsubstituted aurones were weak inhibitors; however, derivatives with two or three hydroxyl groups preferably at 4,6 and 4' positions are able to induce significant tyrosinase inhibition. The most potent aurone was found to be the naturally occurring 4,6,4'-trihydroxyaurone which induces 75% inhibition at 0.1 mM concentration and is highly effective when compared to kojic acid, one of the best tyrosinase inhibitors known so far (the latter is completely inactive at such concentrations). Active aurones are devoid of toxic effects as shown by in vivo studies.

• Authors: Sabrina Okombi, Delphine Rival, Sébastien Bonnet, Anne-Marie Mariotte, Eric Perrier, Ahcène Boumendjel
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 1 Pg. 329-33 (Jan 12 2006) ISSN: 0022-2623 [Print] United States
• PMID: 16392817 (Publication Type: Journal Article)

Chemical References

• Benzofurans
• Enzyme Inhibitors
• aurone
• Monophenol Monooxygenase

Topics

• Administration, Oral
• Animals
• Benzofurans (administration & dosage, chemical synthesis, pharmacology)
• Cell Survival (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (administration & dosage, chemical synthesis, pharmacology)
• Female
• Humans
• In Vitro Techniques
• Melanocytes (cytology, drug effects, enzymology)
• Molecular Structure
• Monophenol Monooxygenase (antagonists & inhibitors)
• No-Observed-Adverse-Effect Level
• Rabbits
• Rats
• Skin (drug effects)