Analogues of N-hydroxy-N'-phenylthiourea and N-hydroxy-N'-phenylurea as inhibitors of tyrosinase and melanin formation

Marc Criton; Véronique Le Mellay-Hamon

doi:10.1016/j.bmcl.2008.04.079

Analogues of N-hydroxy-N'-phenylthiourea and N-hydroxy-N'-phenylurea as inhibitors of tyrosinase and melanin formation

Bioorg Med Chem Lett. 2008 Jun 15;18(12):3607-10. doi: 10.1016/j.bmcl.2008.04.079. Epub 2008 May 4.

Authors

Marc Criton¹, Véronique Le Mellay-Hamon

Affiliation

¹ Mayoly Spindler S.A. Laboratory, Preclinical R&D, 6, avenue de l'Europe-BP51, 78401 Chatou cedex, France.

PMID: 18501598
DOI: 10.1016/j.bmcl.2008.04.079

Abstract

A series of N-hydroxy-N'-phenylthiourea and N-hydroxy-N'-phenylurea analogues were prepared and evaluated as inhibitors of tyrosinase and melanin formation. The most active analogue 1 inhibited mushroom tyrosinase with an IC(50) of around 0.29 microM and also retained a substantial potency in cell culture by reducing pigment synthesis by 78%. Therefore, compound 1 could be considered as a promising candidate for preclinical drug development for skin hyperpigmentation application.

MeSH terms

Agaricales / enzymology
Animals
Cell Line, Tumor
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Melanins / antagonists & inhibitors*
Melanins / biosynthesis
Melanocytes / drug effects*
Melanocytes / enzymology
Melanoma
Mice
Molecular Structure
Monophenol Monooxygenase / chemistry
Monophenol Monooxygenase / drug effects*
Peptides / chemical synthesis
Peptides / chemistry
Peptides / pharmacology*
Phenylthiourea / analogs & derivatives*
Phenylthiourea / chemistry
Phenylthiourea / pharmacology*
Stereoisomerism
Structure-Activity Relationship
Toxicity Tests

Substances

Melanins
Peptides
Phenylthiourea
Monophenol Monooxygenase