Tyrosinase (TYR) is a copper-containing transmembrane polyphenol oxidase widely distributed in a variety of species, ranging from bacteria, higher plants, fungi, and insects to mammals. TYR controls the biosynthetic pathway of a natural pigment, melanin [1]: either overproduction or deficiency of melanin can lead to diseases. In humans, melanin overproduction can cause skin complications such as melasma and ephelides, as well as the severe skin cancer melanoma. Therefore, tyrosinase inhibitors have been widely applied in cosmetics and are considered as potential for the treatment of melanoma.
Currently, several tyrosinase inhibitors, including resorcinol, hydroquinone, arbutin and kojic acid are used for cosmetic depigmentation. However, resorcinol and hydroquinone are potential allergens, and can only be applied on intact skin. Arbutin and kojic acid have been reported to trigger contact dermatitis and both compounds have mutagenicity, and tumor-promoting activity in animal model, leading to arbutin being banned in some countries since 2001 [2,3,4]. Furthermore, all these inhibitors are more potent against mushroom tyrosinase than human tyrosinase, as the former enzyme is generally used for testing due to lack of availability of the human form.
Thus, there is a demand to develop novel tyrosinase inhibitors with improved activity against human TYR. Here, we report design and synthesis of new conjugated compounds linking known binding motifs, which could serve as a foundation structure for the further improvement.