In vitro and in silico studies of the inhibitory effects of some novel kojic acid derivatives on tyrosinase enzyme

Abstract

<strong><em>Objective(s):</em></strong> Tyrosinase is a key enzyme in pigment synthesis. Overproduction of melanin in parts of the skin results in hyperpigmentation diseases. This enzyme is also responsible for the enzymatic browning in fruits and vegetables. Thus, its inhibitors are of great importance in the medical, cosmetic and agricultural fields. <br/><strong><em>Materials and Methods</em></strong><strong><em>: </em></strong>A series of twelve kojic acid derivatives were designed to be evaluated as tyrosinase activity inhibitors. The potential inhibitory activity of these compounds was investigated <em>in silico </em>using molecular docking simulation method. Four compounds with a range of predicted tyrosinase inhibitory activities were prepared and their inhibitory effect on tyrosinase activity was evaluated. The antioxidant properties of these compounds were also investigated by <em>in vitro</em> DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydrogen peroxide scavenging assays. <br/><strong><em>Results:</em></strong> Compound <strong>IIId</strong> exhibited the highest tyrosinase inhibitory activity with an IC₅₀ value of 0.216 ± 0.009 mM which was in accordance with the <em>in silico</em> ΔG_bind results (-13.24 Kcal/mol). <strong><em>Conclusion: </em></strong>Based on the docking studies, from the twelve compounds studied, one <strong>(IIId)</strong> appeared to have the highest inhibition on tyrosinase activity. This was confirmed by enzyme activity measurements. Compound <strong>IIId</strong> has an NO₂ group which binds to both of Cu²⁺ ions located inside the active site of the enzyme. This compound appeared to be even stronger than kojic acid in inhibiting tyrosinase activity. The DPPH free radical scavenging ability of all the studied compounds was more than that of BHT. However, they were not as strong as BHT or gallic acid in scavenging hydrogen peroxide.