Synthesis, biological evaluation, molecular docking, MD simulation and DFT analysis of new 3-hydroxypyridine-4-one derivatives as anti-tyrosinase and antioxidant agents.

In the present study, ten new substituted 3-hydroxypyridine-4-one derivatives were synthesized in a four-step method, and their chemical structures were confirmed using various spectroscopic techniques. Subsequently, the inhibitory activities of these derivatives against tyrosinase enzyme and their antioxidant activities were evaluated. Amongest the synthesized compounds, bearing a 4-OH-3-OCH substitution was found to be a promising tyrosinase inhibitor with an IC value of 25.82 μM, which is comparable to the activity of kojic acid as control drug. Kinetic study indicated that compound is a competitive inhibitor of tyrosinase enzyme, which was confirmed by molecular docking results. The molecular docking study and MD simulation showed that compound was properly placed within the tyrosinase binding pocket and interacted with key residues, which is consistent with its biological activity. The DFT analysis demonstrated that compound is kinetically more stable than the other compounds. In addition, compounds and exhibited the best antioxidant activities. The findings indicate that compound could be a promising lead for further studies.