Inhibitory Effects,\nFluorescence Studies, and Molecular\nDocking Analysis of Some Novel Pyridine-Based Compounds on Mushroom\nTyrosinase

Melanin biosynthesis in different organisms is performed\nby a tyrosinase\naction. Excessive enzyme activity and pigment accumulation result\nin different diseases and disorders including skin cancers, blemishes,\nand darkening. In fruits and vegetables, it causes unwanted browning\nof these products and reduces their appearance quality and economic\nvalue. Inhibiting enzyme activity and finding novel powerful and safe\ninhibitors are highly important in agriculture, food, medical, and\npharmaceutical industries. In this regard, in the present study, some\nnovel synthetic pyridine-based compounds including 2,6-bis (tosyloxymethyl)\npyridine (compound <b>3</b>), 2,6-bis (butylthiomethyl) pyridine\n(compound <b>4</b>), and 2,6-bis (phenylthiomethyl) pyridine\n(compound <b>5</b>) were synthesized for the first time, and\ntheir inhibitory potencies were assessed on mushroom tyrosinase diphenolase\nactivity. The results showed that while all tested compounds significantly\ndecreased the enzyme activity, compounds <b>4</b> and <b>5</b> had the highest inhibitory effects (respectively, 80 and\n89% inhibition with the IC<sub>50</sub> values of 17.0 and 9.0 μmol\nL<sup>–1</sup>), and the inhibition mechanism was mixed-type\nfor both compounds. Ligand-binding studies were carried out by fluorescence\nquenching and molecular docking methods to investigate the enzyme–compound\ninteractions. Fluorescence quenching results revealed that the compounds\ncan form nonfluorescent complexes with the enzyme and result in quenching\nof its intrinsic emission by the static process. Molecular docking\nanalyses predicted the binding positions and the amino acid residues\ninvolved in the interactions. These compounds appear to be suitable\ncandidates for more studies on tyrosinase inhibition.