Publication: Discovery of bis-thiourea derivatives as potent tyrosinase inhibitors: combined experimental and computational study
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Issued Date
2025-01-01
Resource Type
ISSN
14756366
eISSN
14756374
Scopus ID
2-s2.0-105009502120
Journal Title
Journal of Enzyme Inhibition and Medicinal Chemistry
Volume
40
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Enzyme Inhibition and Medicinal Chemistry Vol.40 No.1 (2025)
Suggested Citation
Sabuakham S., Nasoontorn S., Nuramrum N., Silsirivanit A., Rungrotmongkol T., Pingaew R., Mahalapbutr P. Discovery of bis-thiourea derivatives as potent tyrosinase inhibitors: combined experimental and computational study. Journal of Enzyme Inhibition and Medicinal Chemistry Vol.40 No.1 (2025). doi:10.1080/14756366.2025.2518195 Retrieved from: https://hdl.handle.net/20.500.14740/21164
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Abstract
Tyrosinase, a key enzyme in melanin synthesis, serves as a primary target for developing depigmenting agents. The search for novel tyrosinase inhibitors is needed due to the adverse effects of current inhibitors. This study evaluated 16 bis-thiourea derivatives using in vitro and in silico methods, identifying compound 4, with chlorine substituents, as the most potent inhibitor. Compound 4 outperformed kojic acid in inhibiting mushroom tyrosinase activity and interacted with catalytic copper ions and active site residues, as revealed by molecular docking and copper-chelating assay. Molecular dynamics simulation and MM/PBSA-based free energy calculations confirmed the greater stability and binding affinity of the compound 4-tyrosinase complex in an aqueous environment compared to kojic acid-tyrosinase complex. Melanin assay revealed that compound 4 significantly suppressed melanin production in B16F10 melanoma cells, showing stronger anti-melanogenic activity than kojic acid. Drug-likeness predictions confirmed its compliance with Lipinski’s rule of five, supporting bis-thiourea derivatives as promising tyrosinase inhibitors.