Synthesis and Evaluation of Novel Tyrosinase Inhibitors

Melanin is responsible for the protection against ultraviolet light and the pigmentation of mammalian skin, hair, and eyes.1–3 This indolic polymer is located in the epidermis of mammals and is produced through melanogenesis in specialized cells called melanocytes. Over production of melanin in humans can produce unwanted aesthetic products such as dark spots, freckles, solar lentigo (age spots), melasma, and even cancer.2,4,5 The overproduction of melanin during post-harvest handling causes enzymatic browning of produce resulting in a loss of nutritional value, a decrease in shelf life, and a decline flavor.2,6–8 Tyrosinase is an oxidoreductase, type-3, copper-containing glycoprotein located in the membrane of a melanosome. This enzyme catalyzes three steps in the production of melanin, one of which is the rate limiting step of the biosynthetic process.9,10 Melanogenesis, is initiated by the oxidation of L-tyrosine (monophenol) and/or dopaquinone/L-DOPA (diphenol) to dopaquinone by the key enzyme tyrosinase. 1,11Through the inhibition and regulation of tyrosinase, a crucial enzyme in the process of melanogenesis, pharmaceutical, cosmetic, and agricultural industries are developing inhibitory mechanisms to modulate the production and concentration of melanin with hopes to combat the effects of browning in the skin of humans and produce alike. Currently the disruption of melanogenesis through the synthetic or natural inhibition of tyrosinase is the most popular approach. Thalassotalic acid A-C, a series of natural products isolated from the marine bacterium Thalassotalea in 2016, was shown to have high inhibitory activity against tyrosinase compared to popular inhibitors such as kojic acid, arbutin, aloesin, and hydroquinone.8 This research hopes to further optimize and evaluate Thalassotalic acid A by synthesizing analogues with metal chelating and hydrophobic groups, properties that are known to have high inhibitory rates against mushroom and human tyrosinase