Evaluation of quercetin omega-6 and -9 esters on activity and structure of mushroom tyrosinase: Spectroscopic and molecular docking studies.

Abstract

Quercetin is one of the most ubiquitous dietary flavonoids widely distributed in plants and foods of plant origin, and is a potent tyrosinase inhibitor. Quercetin fatty esters could lead to an improve in quercetin lipophilicity which could positively affect its pharmacological activity. In this study, the inhibitory effect of two novel esters of quercetin-linoleic acid (ligand A) and quercetin-oleic acid (ligand B) has been investigated on structure and diphenolase activity of mushroom tyrosinase (MT) by experimental and molecular docking techniques. The inhibitory kinetics study using UV-visible spectrophotometry in the presence of its substrate 3,4-dihydroxyphenylalanine (L-dopa), revealed that both esters successfully inhibit the activity of tyrosinase and reduce the formation of dopaquinone. Results showed that the binding of ligands to MT induced rearrangement and conformational changes of the enzyme. Thermodynamic parameters of these interactions (Ka , ∆G°, ∆H° and ∆S°) were obtained at pH=6.8 and temperatures of 298 and 310K. Molecular docking studies further was applied to calculation of binding energies (ΔGbA =-21.84kJ/mol, ΔGbB =-20.92kJ/mol), inhibition constant values (KIA =160µM, KIB =220µM) and the special binding site. It can be deduced that ligands act as a potential tyrosinase inhibitor and it was found that the best possible interaction condition with binding modes visualize was achieved by ligand A and exhibited the potent tyrosinase inhibitory activity. These findings may be helpful to understand the inhibition mechanism of quercetin fatty acids esters on tyrosinase and provide a convenient screening method to differentiate phenolic tyrosinase inhibitors. PRACTICAL APPLICATIONS: Bioavailability and antioxidant activity of conjugated fatty acids with their bioequivalence in several biological effects and metabolic processes such as beta-oxidation from various forms has been reported to be highly variable and useful. Quercetin shows beneficial role in human health, but its biological effects in vivo is limited by poor bioavailability, low skin permeability and solubility. This study design new tyrosinase inhibitors which helpful to functional research of unsaturated fatty acid esters in the treatment of inflammatory diseases and hyperpigmentation disorders. In addition, undesirable enzymatic browning of plant derived-foods by tyrosinase causes a decrease in market value and economic loss of food products. The results suggest that the conjugation of quercetin with linoleic and oleic acids resulted in novel stronger tyrosinase inhibitors which may have therapeutic applications and replacement of toxic tyrosinase inhibitors and contribute as anti- browning agents in food, cosmetic and pharmaceutical industry.