In silico assessment of the inhibitory effect of four flavonoids (Chrysin, Naringin, Quercetin, Kaempferol) on tyrosinase activity using the MD simulation approach

Abstract

Tyrosinase is a tetrameric enzyme that plays an important role in pigment production. Overproduction of melanin, which may lead to several skin disorders, is a result of tyrosinase activity. Hence, tyrosinase inhibitors are of key importance in the treatment of these disorders. In the present study, four flavonoid inhibitors, namely chrysin, naringin, quercetin, and kaempferol, were evaluated physiochemically, and the inhibitory effects of these compounds on tyrosinase activity were evaluated using the molecular dynamics (MD) simulation method. To create the best conformation of the enzyme-substrate/inhibitor, the docking process for enzyme-substrate, i.e., enzymechrysin, enzyme-quercetin, enzyme-naringin, and enzyme-kaempferol, was performed. The complexes with the best binding energies were selected as the models for the MD simulation process. Furthermore, the structural (RMSD, Rg, RMSF, and Distance) and the thermodynamics properties of the complexes were evaluated. Additionally, the PMF was conducted to calculate the binding free energies. The results showed that chrysin, quercetin and the substrate were at similar distances to the amino acids of the active site, but naringin and kaempferol were closer to the active site of the enzyme than the substrate. Moreover, the analysis of the binding energy revealed that the substrates, chrysin, kaempferol, quercetin, and naringin bound to the enzyme with binding energies of !7.8, !3.1, !7.1, !3.9, and !8.4 kcal/mol, respectively, which confirms that naringin has the highest inhibitory effect on tyrosinase among other inhibitors, which makes it an appropriate candidate as a whitening agent in skin disorders.

Structural and inhibitory effects of fulvic and humic acids against tyrosinase

“…The value of RMSF offers a better knowledge about tyrosinase structural fluctuations as well as its flexibility (Farasat et al, 2020).…”

“…Additionally, to study FA–tyrosinase and HA–tyrosinase interactions, RMSD (Root Mean Square Deviation) and RMSF (Root Mean Square Fluctuation) were measured utilizing GRO‐MACS software through the simulation. Subsequently, to achieve the final PDB file of the MD simulation procedure, the Pymol software was utilized (Farasat et al, 2020; Gheibi et al, 2020).…”

A Unique Acylated Flavonol Glycoside from Prunus persica (L.) var. Florida Prince: A New Solid Lipid Nanoparticle Cosmeceutical Formulation for Skincare

“…In general, flavonoid-metal complexes with metalloenzymes have shown the potential to be SOD mimetics [ 67 ]. Chrysin, naringin, quercetin, and kaempferol, the core of KDPAG showed tyrosinase inhibitory effects [ 68 ]. Flavonols, the class of our new isolate, kaempferol, quercetin, and myricetin were reported to possess anti-elastase and anti-collagenase activity [ 67 , 69 ].…”

Biotechnological Applications and Health-Promoting Properties of Flavonols: An Updated View

“…Flavonols have recently attracted considerable interest for their ability to confer defense against UV radiation-induced skin damage through both direct photoabsorption and antioxidant activity [99] and prevent skin aging and hyperpigmentation caused by solar UV irradiation [100].…”

“…In addition, a new acylated kaempferol glycoside with a rare structure, kaempferol 3-O-β4C1-(6"-O-3,4-dihydroxyphenylacetyl glucopyranoside), which has been isolated from Prunus persica (L.), kaempferol, quercetin and myricetin were reported to have antielastase and anti-collagenase activity [102][103][104]. Kaempferol and quercetin also have an inhibitory effect on tyrosinases [100]. Inhibiting the three enzymes, collagenases, elastases and tyrosinases, which are known to play a crucial role in skin aging, increases the strength of the skin, improves elasticity and helps to avoid development of dark spots, preventing the formation of wrinkles [102].…”