Depigmenting Potency of Hydroquinone Fatty Acid Esters on the Skin

In order to improve the oxidative stability of hydroquinone (HQ), the only depigmenting agent available clinically for skin, 14 hydroquinone fatty acid esters (HQ-Rs) were synthesized and examined for their stability, efficacy, and intradermal metabolism. HQ-Rs containing more than 3 carbon atoms in the fatty acid side chain showed excellent stability in an aqueous base (pH 6). HQ-Rs containing fewer than 8 carbon atoms in the fatty acid side chain exhibited skin depigmenting potencies better than that of HQ. HQ-R was quantitatively hydrolyzed by a skin homogenate to liberate HQ. The hydrolysis velocity of the HQ-Rs was dependent on the length of the fatty acid side chain; the longer the length, the slower the hydrolysis velocity. From these results, we concluded that HQ-R is absorbed into the skin after topical application, hydrolyzed by esterase, and it depigments the skin by liberating HQ. Thus, HQ-R function as a prodrug of HQ; it exhibits both an excellent oxidative stability and an excellent skin depigmenting potency by liberating HQ within the skin.