Synthesis and biochemical evaluation of 5-(pyridin-4-yl)-4H-1,2,4-triazol-4-amine-based inhibitors of tyrosinase from Agaricus bisporus

Several studies demonstrated that hyperpigmentation pathologies might be treated by using agents targeting the enzymatic metallo-protein tyrosinase. Therefore, we predicted the development of a series of small molecules able to inhibit diphenolase activity of tyrosinase from Agaricus bisporus. The designed compounds were readily synthesized by S-alkylation and the synthesized compounds were tested through biochemical screening, thus providing structure-affinity relationships for this class of 5-(pyridin-4-yl)-3-(alkylsulfanyl)-4H- 1,2,4-triazol-4-amine derivatives. In addition, docking simulations suggested the binding mode within the catalytic site of the targeted enzyme