Rational Design and Synthesis of 4-O-Substituted Phenylmethylenethiosemicarbazones as Novel Tyrosinase Inhibitors

Abstract

In continuing our program aimed to search for tyrosinase inhibitors, a series of novel 4-O-substituted phenylmethylenethiosemicarbazones were rational designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were also evaluated. A fair number of compounds were found to have significant tyrosinase inhibitiory activity. Particularly, the IC₅₀ values of compounds 3a—g, 3j and 3s were of the same magnitude as tropolone, one of the best tyrosinase inhibitors known so far. Furthermore, the structure–activity relationships of these compounds were also investigated. All these data suggested that these molecules might be utilized for the development of new candidate for the treatment of dermatological disorders, and further development of such compounds may be of interest.