Skin permeation and comparative evaluation of gentisic acid ester derivatives as skin-lightening agents

Gentisic acid (GA) derivatives are known to exhibit inhibitory activity against tyrosinase. Skin permeation of five GA derivatives have been evaluated and correlated with their tyrosinase inhibition and cytotoxicity. All compounds tested were stable at 37 °C up to 12 h. Skin permeation study in mice showed the highest permeation rate for the methyl derivative, MG (232.0033 μg/cm2/h) over GA (172.0852 μg/cm2/h), followed by the ethyl derivative, EG (182.9242 μg/cm2/h). Although all the esters tested were more cytotoxic to melanocytes than GA, MG was the least cytotoxic among the five esters. MG and EG also showed similar mushroom tyrosinase inhibition to gentisic acid (IC50 176 μg/mL). MG showed the highest skin permeation rate among the GA derivatives tested, and was considered a promising candidate together with EG based on the tyrosinase inhibition and melanocyte cytotoxicity.