Tyrosinase Inhibitory Effects of Derivatives of (E)‐2‐(Substituted Benzylidene)‐3,4‐Dihydronaphthalen‐1(2H)‐One

Abstract

Tyrosinase plays an essential role in melanin biosynthesis, and as such it has received great attention as a key target for the treatment of pigmentation disorders. In our earlier studies, we explored analogs with the β‐phenyl‐α,β‐unsaturated carbonyl template, and the results obtained indicated that this template confers potent tyrosinase inhibitory activity. Thus, in the present study, (E)‐2‐(substituted benzylidene)‐3,4‐dihydronaphthalen‐1(2H)‐one derivatives (compounds 1–6) with this template were synthesized and investigated with respect to their mushroom tyrosinase inhibitory effects. Derivative 4 with a 3‐hydroxy‐4‐methoxyl substituent on the β–phenyl ring of the template inhibited mushroom tyrosinase fourfold more than kojic acid (IC50 = 15.60 ± 0.32 μM vs. 57.06 ± 0.46 μM). In silico docking simulation supported this potent inhibitory activity of compound 4 by demonstrating a binding energy of −6.4 kcal/mol at the active site of mushroom tyrosinase. Kinetic results imply that 4 competitively inhibits mushroom tyrosinase.