Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation.

Excessive melanin deposition may lead to a series of skin disorders. The production of melanin is carried out by melanocytes, in which the enzyme tyrosinase performs a key role. In this work, we identified a series of novel tyrosinase inhibitor hybrids with a dihydrochalcone skeleton and resorcinol structure, which can inhibit tyrosinase activity and reduce the melanin content in the skin. Compound possessed the most potent activity against tyrosinase, showing IC values at nanomolar concentration ranges, along with significant antioxidant activity and low cytotoxicity. Furthermore, permeation tests, supported by HPLC analysis and 3D OrbiSIMS imaging visualization, revealed the excellent permeation of . More importantly, compound reduced the melanin content on UV-induced skin pigmentation in a guinea pig model . These results suggest that compound may serve as a promising potent tyrosinase inhibitor for the development of a potential therapy to treat skin hyperpigmentation.