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.

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

Rosaria Gitto;Antonella Fais;Sonia Floris;
2020-01-01

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.
2020
MTT assays; docking studies; drug design; structure-activity relationships; tyrosinase inhibitors.
File in questo prodotto:
File Dimensione Formato  
2020 ChemMedChem.pdf

accesso aperto

Tipologia: versione editoriale
Dimensione 1.03 MB
Formato Adobe PDF
1.03 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/295217
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 17
social impact