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

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 beta-phenyl-alpha,beta-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 (compounds1-6)with this template were synthesized and investigated with respect to their mushroom tyrosinase inhibitory effects. Derivative4with a 3-hydroxy-4-methoxyl substituent on the beta-phenyl ring of the template inhibited mushroom tyrosinase fourfold more than kojic acid (IC50= 15.60 +/- 0.32 mu M vs. 57.06 +/- 0.46 mu M).In silicodocking simulation supported this potent inhibitory activity of compound4by demonstrating a binding energy of -6.4 kcal/mol at the active site of mushroom tyrosinase. Kinetic results imply that4competitively inhibits mushroom tyrosinase.