Structural requirement of phenylthiourea analogs for their inhibitory activity of melanogenesis and tyrosinase

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6824-8. doi: 10.1016/j.bmcl.2011.09.024. Epub 2011 Sep 13.

Abstract

Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in melanoma B16 cells of 1-phenylthioureas could be the result of inhibition of tyrosinase. However, 1,3-diaryl or 1-phenyl-3-alkylthioureas, 2a-k, appears as melanogenic inhibitor without inhibition of tyrosinase. The molecular docking study of 1e and 2b to binding pocket of tyrosinase provided convincing explanation regarding the necessity of direct connection of planar phenyl to thiourea unit without N'-substitution of phenylthioureas 1 as tyrosinase inhibitor and 2 as non-tyrosinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / enzymology
  • Animals
  • Catalytic Domain
  • Cell Line, Tumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Melanins / antagonists & inhibitors*
  • Melanins / metabolism*
  • Melanoma, Experimental / metabolism
  • Models, Molecular
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / chemistry
  • Monophenol Monooxygenase / metabolism*
  • Phenylthiourea / analogs & derivatives*
  • Phenylthiourea / pharmacology*

Substances

  • Enzyme Inhibitors
  • Melanins
  • Phenylthiourea
  • Monophenol Monooxygenase