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

Abstract

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~c29) was synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, HRMS, and FT-IR, respectively. The biological evaluation results showed that all compounds c1~c29 exhibited definite tyrosinase inhibitory activity; especially, compound c27 was the strongest tyrosinase inhibitor (IC50: 3.07 ± 0.26 μM), being ~4.6-fold stronger than the positive control, kojic acid (IC50: 14.15 ± 0.46 μM). Inhibition kinetic studies validated compound c27 as a reversible mixed-type inhibitor against tyrosinase. Three-dimensional 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.

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

“…The tyrosinase inhibitory activities of compounds 5a~5z were determined according to previous reports [34,35]. In brief, 10 µL of compound was added into 140 µL of tyrosinase, incubated for 5 min at room temperature.…”

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

“…As a therapeutic target, tyrosinase is one important metal enzyme containing two copper, which widely presents in the organism ( Min et al, 2023 ; Fan et al, 2017 ). Tyrosinase has been confirmed to be involved in the synthesis of melanin ( Li et al, 2023 ; Hassan et al, 2023 ; Li J. et al, 2021 ). The first reaction process is monophenolase activity, in which L-tyrosine is hydroxylated into L-dopa and the second reaction process is diphenolase activity, in which L-dopa is subsequently oxidized into dopaquinone ( Djafarou et al, 2023 ; Lee et al, 2023 ; Zargaham et al, 2023 ).…”