Analogs of 5-(substituted benzylidene)hydantoin as inhibitors of tyrosinase and melanin formation.

Abstract

BACKGROUND:

Many tyrosinase inhibitors find application in cosmetics and pharmaceutical products for the prevention of the overproduction of melanin in the epidermis. A series of 5-(substituted benzylidene)hydantoin derivatives 2a-2k were prepared, and their inhibitory activities toward tyrosinase and melanin formation were evaluated.

METHODS:

The structures of the compounds were established using (1)H and (13)C NMR spectroscopy and mass spectral analyses. All the synthesized compounds were evaluated for their mushroom tyrosinase inhibition activity.

RESULTS:

The best results were obtained for compound 2e which possessed hydroxyl group at R(2) and methoxy group at R(3), respectively. We predicted the tertiary structure of tyrosinase, simulated its docking with compound 2e and confirmed that this compound interacts strongly with mushroom tyrosinase residues as a competitive tyrosinase inhibitor. In addition, we found that 2e inhibited melanin production and tyrosinase activity in B16 cells.

CONCLUSIONS:

Compound 2e could be considered as a promising candidate for preclinical drug development in skin hyperpigmentation applications.

GENERAL SIGNIFICANCE:

This study will enhance understanding of the mechanism of tyrosinase inhibition and will contribute to the development of effective drugs for use hyperpigmentation.

• Authors: Young Mi Ha, Jin-Ah Kim, Yun Jung Park, Daeui Park, Ji Min Kim, Ki Wung Chung, Eun Kyeong Lee, Ji Young Park, Ji Yeon Lee, Hye Jin Lee, Jeong Hyun Yoon, Hyung Ryong Moon, Hae Young Chung
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1810 Issue 6 Pg. 612-9 (Jun 2011) ISSN: 0006-3002 [Print] Netherlands
• PMID: 21397665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Benzylidene Compounds
• Enzyme Inhibitors
• Hydantoins
• Melanins
• Monophenol Monooxygenase

Topics

• Agaricales (enzymology)
• Benzylidene Compounds (chemical synthesis, chemistry, pharmacology)
• Cell Survival
• Cells, Cultured
• Computer Simulation
• Dose-Response Relationship, Drug
• Drug Design
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Hydantoins (chemical synthesis, chemistry, pharmacology)
• Inhibitory Concentration 50
• Magnetic Resonance Spectroscopy
• Melanins (antagonists & inhibitors, biosynthesis)
• Models, Molecular
• Molecular Structure
• Monophenol Monooxygenase (antagonists & inhibitors)