4-Fluorobenzylpiperazine-containing derivatives as efficient inhibitors of mushroom tyrosinase

Serena Vittorio;Laura Ielo;Salvatore Mirabile;Rosaria Gitto;Antonella Fais;Sonia Floris;Antonio Rapisarda;Maria Paola Germanò;Laura De Luca

2020-01-01

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Abstract

Tyrosinase is a type 3 copper protein involved in the biosynthesis of melanin pigments, therefore the inhibition of its enzymatic activity represents a promising strategy for the treatment of hyperpigmentation-related disorders. To address this point at issue we have previously designed a class of 4-(4-fluorobenzyl)piperazin-1-yl-based compounds proving to be more active inhibitor against tyrosinase from mushroom Agaricus bisporus when compared to positive control kojic acid. Herein, we report the synthesis of further series of 4-(4-fluorobenzyl)piperazin-1-yl-analogs bearing a (hetero)aromatic fragment as key feature to improve protein affinity. The new synthesized compounds were in vitro assayed proving to be potent inhibitors in low micromolar range. Then, the active 2-thienyl and 2-furyl derivatives were selected for further modifications considering their binding mode analyzed by docking studies and their satisfactory safety profiles.