Effect of Hydrophobic D-Glucosamine Analogues on Production of Hyaluronan in Human Keratinocyte and Structural Activity

Abstract

D-Glucosamine (GlcN) (1) , N-acetyl-D-glucosamine (GlcNAc) (2) , and alkyl N-acetyl-β-D-glucosaminide are known to stimulate the production of hyaluronan production in human keratinocyte. Novel hydrophobic derivatives 1 and 2 were synthesized, and the effect of these derivatives on the production of hyaluronan in human keratinocyte was investigated. While GlcN had no effect on the production of hyaluronan in the keratinocyte, N-butyryl-β-D-glucosamine (4) stimulated production. To investigate the mechanism of this stimulation, four subgroups of derivatives of N-acetyl-β-D-glucosaminide were synthesized that contained alkyl alcohols, fluoro alcohols, silyl alcohols, and aromatic alcohols, respectively (10-15). Correlation of Log P (o/w) of the alcohol moieties and hyaluronan production was investigated. The production ratio of hyaluronan to the control experiments increased with an increase of Log P values within each subgroup. However, no correlation was observed between these four subgroups, suggesting that other factors are related to the stimulation of hyaluronan production.