4-Fluorobenzylpiperazine-Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase
| Autor: | Serena Vittorio, Rosaria Gitto, Antonio Rapisarda, Sonia Floris, Laura Ielo, Salvatore Mirabile, Laura De Luca, Antonella Fais, Maria Paola Germanò |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Copper protein
drug design Tyrosinase Agaricus 01 natural sciences Biochemistry Piperazines Melanin Dose-Response Relationship chemistry.chemical_compound Structure-Activity Relationship Drug Discovery MTT assays Structure–activity relationship General Pharmacology Toxicology and Pharmaceutics tyrosinase inhibitors Enzyme Inhibitors docking studies structure-activity relationships Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Monophenol Monooxygenase Organic Chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme chemistry Docking (molecular) Molecular Medicine Drug Kojic acid Agaricus bisporus |
| Popis: | 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, we previously designed a class of 4-(4-fluorobenzyl)piperazin-1-yl-based compounds, which proved to be more active inhibitors against tyrosinase from mushroom Agaricus bisporus than the positive control kojic acid. Herein, we report the synthesis of further series of 4-(4-fluorobenzyl)piperazin-1-yl analogues bearing a (hetero)aromatic fragment as key feature to improve protein affinity. The newly synthesized compounds were assayed in vitro and proved to be potent inhibitors in the low-micromolar range. The active 2-thienyl and 2-furyl derivatives were selected for further modification to allow their binding mode to be analyzed by docking studies and to give satisfactory safety profiles. |
| Databáze: | OpenAIRE |
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