Design, synthesis, and evaluation of beta-galactosylceramide mimics promoting beta-glucocerebrosidase activity in keratinocytes

Bioorg Med Chem Lett. 2003 Mar 10;13(5):813-5. doi: 10.1016/s0960-894x(03)00006-4.

Abstract

We have established an efficient synthesis of mimics of beta-galactosylceramide (beta-GalCer) increasing a beta-glucocerebrosidase (beta-GlcCer'ase) activity that associates with the skin barrier function. Among the synthetic beta-GalCer analogues (6a-6e) described herein, compound 6e exhibited a potent effect on the activation of beta-GlcCer'ase function in vitro and reduced the transepidermal water loss (TEWL) level in a UVB-induced barrier disrupted mice model. These findings indicated that compound 6e could be useful for cosmetics and medicines to improve skin barrier function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetic Materials / chemical synthesis*
  • Biomimetic Materials / pharmacology*
  • Cells, Cultured
  • Drug Design
  • Enzyme Activation / drug effects
  • Epidermis / drug effects
  • Epidermis / metabolism
  • Epidermis / radiation effects
  • Galactosylceramides / chemical synthesis*
  • Galactosylceramides / pharmacology*
  • Glucosylceramidase / metabolism*
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / enzymology
  • Keratinocytes / radiation effects
  • Mice
  • Structure-Activity Relationship
  • Ultraviolet Rays
  • Water Loss, Insensible / drug effects
  • Water Loss, Insensible / radiation effects

Substances

  • Galactosylceramides
  • Glucosylceramidase