Synthesis, biological evaluation, and molecular docking analysis of novel 1, 3, 4-thiadiazole -based kojic acid derivatives as tyrosinase inhibitors

Abstract

Kojic acid is a natural tyrosinase inhibitor that has been clinically used to cure hyperpigmentation in humans. However, kojic acid as a hydrophilic small-molecule has deficient inhibitory activity and stability. In this current work, a new series of kojic acid derivatives, 4a–h bearing 2-amino-5-mercapto-1,3,4-thiadiazole, were synthesized using TBTU as the catalyst, and their chemical structures were characterized by spectroscopic methods. The inhibitory activities of synthesized compounds against Mushroom tyrosinase were evaluated in vitro, and some derivatives showed potent anti-tyrosinase activity. In particular, compounds 4g (IC50=10.71 ± 2.47 µM) and 4h (IC50=18.62 ± 3.05 µM) were comparable with the reference compound, kojic acid (IC50=23.14 µM). The Docking study was in good agreement with experimental results and indicated that compound 4g interacted entirely with the active site of tyrosinase with proper binding energy and mode.