Design, synthesis, biological evaluation, and molecular docking study of thioxo-2,3-dihydroquinazolinone derivative as tyrosinase inhibitors

• A series of thioxo-2,3-dihydroquinazolinone derivatives were designed and synthesized as tyrosinase inhibitors. • The most potent derivative, 4m , depicted anti-tyrosinase activities with an IC 50 value of 9.30 µM. • 4m as the most active compound illustrated mixed inhibition pattern in the kinetic study. Tyrosinase is known to be a key enzyme in melanogenesis and hyperpigmentation. In this study, a series of thioxo-dihydroquinazolinone compounds were designed and synthesized as tyrosinase inhibitors. Among the investigated compounds, 4m demonstrated the best inhibitory activity with an IC 50 value of 15.48 µM compared to kojic acid as a positive control with IC 50 value of 9.30 µM. In kinetic evaluation against tyrosinase, 4m depicted a mixed inhibition pattern. Additionally, antioxidant evaluations exhibited moderate to weak potency in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The detailed interactions and binding mode toward tyrosinase of the most potent derivative were explicated by molecular docking study. Moreover, the computer-aided drug-likeness and pharmacokinetic studies were also carried out.