Design, Synthesis and Biological Evaluation of Hydroxy- or Methoxy-Substituted Phenylmethylenethiosemicarbazones as Tyrosinase Inhibitors

A series of hydroxy- or methoxy-substituted phenylmethylenethiosemicarbazones were designed, synthesized and evaluated as mushroom tyrosinase inhibitors. The results demonstrated that most of target compounds had remarkable inhibitory activities on mushroom tyrosinase. Interestingly, compound 2h was found to be the most potent tyrosinase inhibitor with IC50 value of 0.118 mu m. The possible interaction mode between compound 2h and tyrosinase was proposed. In addition, the 1,1-diphenyl-2-pierylhydrazyl (DPPH) radical scavenging activities of select compounds (IC50 <10.0 mu m) were also investigated. Compounds 2d., 2e, 2h, 2i and 21 exhibited more potent DPPH radical scavenging activity than well-known antioxidants ascorbic acid (Vc) and tertiary butyl hydroquinone (TBHQ). These results suggested that such compounds might be utilized for the development of new candidate for treatment of dermatological disorders.