1. 5-Methoxy-2-mercaptobenzimidazole as an efficient inhibitor on tyrosinase: Inhibitory activity and mechanism
- Author
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Wei-Ming Chai, Qi-Ming Wei, Zi-Yi Yu, Mei-Zhen Lin, and Shuang Song
- Subjects
0106 biological sciences ,0301 basic medicine ,Conformational change ,Stereochemistry ,Tyrosinase ,Bioengineering ,Inhibitory postsynaptic potential ,01 natural sciences ,Applied Microbiology and Biotechnology ,Tyrosinase inhibitor ,Hydrophobic effect ,03 medical and health sciences ,010608 biotechnology ,Enzyme Inhibitors ,chemistry.chemical_classification ,2-mercaptobenzimidazole ,Monophenol Monooxygenase ,Hydrogen bond ,Hydrogen Bonding ,Molecular Docking Simulation ,030104 developmental biology ,Enzyme ,chemistry ,Thermodynamics ,Benzimidazoles ,Hydrophobic and Hydrophilic Interactions ,Biotechnology - Abstract
In this study, 5-methoxy-2-mercaptobenzimidazole (5-M-2-MB) was confirmed as an efficient tyrosinase inhibitor by methods of enzyme kinetic, fluorescence quenching, ANS-binding, thermodynamics, energy transfer, and molecular docking in combination. The results proved that 5-M-2-MB significantly inhibited the tyrosinase (IC50 = 60 ± 2 nM) in a reversible and competitive way with the Ki value of 80 ± 1 nM. It quenched the intrinsic fluorescence of tyrosinase through a static mechanism, and caused conformational change of the enzyme by increasing the hydrophobic region. Moreover, this compound could bind to tyrosinase and form 5-M-2-MB-tyrosinase complex by hydrogen bond and hydrophobic interaction. The interactions were generated between 5-M-2-MB and specific amino acid residues (Trp-358, Thr-308, Glu-356, and Asp-357) located on the A chain of tyrosinase. Therefore, this study would offer a theoretical foundation for developing the new tyrosinase inhibitor.
- Published
- 2021