Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid-Eugenol Esters

Tyrosinase plays crucial roles in mediating the production of melanin pigment; thus, its inhibitors could be useful in preventing melanin-related diseases. To find potential tyrosinase inhibitors, a series of cinnamic acid-eugenol esters (c1 similar to c29) was synthesized and their chemical structures were confirmed by H-1 NMR, C-13 NMR, HRMS, and FT-IR, respectively. The biological evaluation results showed that all compounds c1 similar to c29 exhibited definite tyrosinase inhibitory activity; especially, compound c27 was the strongest tyrosinase inhibitor (IC50: 3.07 +/- 0.26 mu M), being similar to 4.6-fold stronger than the positive control, kojic acid (IC50: 14.15 +/- 0.46 mu M). Inhibition kinetic studies validated compound c27 as a reversible mixed-type inhibitor against tyrosinase. Threedimensional fluorescence and circular dichroism (CD) spectra results indicated that compound c27 could change the conformation and secondary structure of tyrosinase. Fluorescence-quenching results showed that compound c27 quenched tyrosinase fluorescence in the static manner with one binding site. Molecular docking results also revealed the binding interactions between compound c27 and tyrosinase. Therefore, cinnamic acid-eugenol esters, especially c27, could be used as lead compounds to find potential tyrosinase inhibitors.

Automated summary

Tyrosinase inhibitors, including cinnamic acid-eugenol esters, especially c27, showed definite inhibitory activity against tyrosinase, which is crucial in melanin production. Compound c27 exhibited the strongest tyrosinase inhibitory activity and could potentially be used as a lead compound in finding tyrosinase inhibitors.