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Identification of (Z)-2-benzylidene-dihydroimidazothiazolone derivatives as tyrosinase inhibitors: Anti-melanogenic effects and in silico studies

Summary

Scientists developed new chemical compounds that can block tyrosinase, an enzyme that produces skin pigment (melanin). These new compounds, called DHIT derivatives, work much better than existing skin lightening agents like kojic acid and appear to be safer. The best compound tested was 100 times more effective at stopping melanin production than kojic acid in laboratory tests and showed no toxicity to cells.

Background

Tyrosinase is the rate-limiting enzyme in melanogenesis and abnormal melanin production causes hyperpigmentation disorders. Many existing tyrosinase inhibitors like kojic acid and hydroquinone have severe side effects including carcinogenicity and dermatitis. Previous research identified benzylidene derivatives with β-phenyl-α,β-unsaturated carbonyl scaffolds as potent tyrosinase inhibitors.

Objective

To design and synthesize 5,6-dihydroimidazo[2,1-b]thiazol-3(2H)-one (DHIT) derivatives based on the structure of MHY773 and evaluate their tyrosinase inhibitory activity and anti-melanogenic effects both enzymatically and in cellular systems.

Results

Three DHIT derivatives (1a, 1b, 1f) inhibited mushroom tyrosinase more than kojic acid, with compound 1b showing 100-fold greater potency than kojic acid (IC50 0.88 μM vs 84.41 μM). Kinetic studies demonstrated 1b and 1f are competitive inhibitors. In B16F10 cells, 1b and 1f significantly inhibited cellular tyrosinase activity and intracellular/extracellular melanin production more potently than kojic acid without cytotoxicity.

Conclusion

DHIT derivatives, particularly 1b and 1f, are promising candidates as anti-browning agents and therapeutic agents for hyperpigmentation disorders. The DHIT template appears to be a useful scaffold for developing novel and potent tyrosinase inhibitors with improved safety profiles compared to existing agents.
  • Published in:Computational and Structural Biotechnology Journal,
  • Study Type:In vitro Research Study with Computational Modeling,
  • Source: PMID: 35242283, DOI: 10.1016/j.csbj.2022.02.007
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