In vitro and in vivo evidence of tyrosinase inhibitory activity of a synthesized (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT)

Abstract

Tyrosinase is a key enzyme that catalyses the initial rate-limiting steps of melanin synthesis. Due to its critical role in melanogenesis, various attempts were made to find potent tyrosinase inhibitors although many were not safe and effective in vivo. We evaluated tyrosinase inhibitory activity of six compounds. Among them, (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT) had the greatest inhibitory effect and potency as the IC₅₀ value of 5-HMT was lower than that of kojic acid, widely-known tyrosinase inhibitor. Based on in silico docking simulation, 5-HMT had a greater binding affinity than kojic acid with a different binding conformation in the tyrosinase catalytic site. Furthermore, its skin depigmentation effect was confirmed in vivo as 5-HMT topical treatment significantly reduced UVB-induced melanogenesis in HRM2 hairless mice. In conclusion, our study demonstrated that 5-HMT has a greater binding affinity and inhibitory effect on tyrosinase and may be a potential candidate for a therapeutic agent for preventing melanogenesis.

Keywords: (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one; HRM2 hairless mice; melanogenesis; tyrosinase inhibitor.