Design, synthesis and evaluation of PEGylated lipoic acid derivatives with functionality as potent anti-melanogenic agents

The novel PEGylated lipoic acid (LA) derivatives with functionality were synthesized in satisfactory yield by simple procedures and evaluated about its anti-melanogenic activity on the B16F10 melanoma cells. Grafting a PEG moiety onto the carboxyl group of LA has reduced the cell cytotoxicity and provided the water solubility and functionality to incorporate the other bioactive moieties. We have found that derivatives showed inhibition of melanin formation by up to 36.5% at 0.1 mM, whereas LA decreased the melanin formation by 8.6%. In addition, it also inhibits at least 86.4% UV-induced MMP-1 expression at 0.1 mM which is higher than LA. These data suggest that the novel PEGylated LA derivatives with functionality may thus serve as a potentially effective anti-melanogenic and anti-aging agent.

The novel PEGylated lipoic acid (LA) derivatives with functionality were prepared for the combination of two pharmacophores on the one molecular scaffold and led to enhanced water solubility and evaluated for its anti-melanogenic activity and UVA-induced MMP-1 expressionFigure optionsDownload as PowerPoint slideHighlights
► The PEGylated lipoic acid (LA) ester derivatives with functionality were synthesized.
► LA derivatives showed good water solubility and low cytotoxicity.
► The anti-melanogenic activity of LA derivatives was evaluated.
► LA derivatives showed significant inhibition effect for MMP-1 expression.