Evaluation of novel pyrimidine derivatives as a new class of mushroom tyrosinase inhibitor

Abstract

Background and aim

Tyrosinase (EC 1.14.18.1) is responsible for enzymatic browning in fruits and vegetables. Its inhibitors may be applied to efficiently treat hyperpigmentation and are widely used in pharmaceutical and cosmetic products, food supplements and insecticides. Previous studies have shown that heterocyclic compounds with an amino group can inhibit tyrosinase activity. The present study aims to evaluate the inhibitory effect of some novel 2,6-diamino-4-chloropyrimidine derivatives (1a-e) and 2,4,6-triaminopyrimidine (2a–e) including bioactive aniline moiety on the activity of the mushroom tyrosinase.

Methods

In practice, the azo salt was initially synthesized from aniline derivatives and combined subsequently with the 2,4,6-triaminopyrimidine and 2,6-diamino-4 chloropyrimidine followed by crystallization. The structures of resulting compounds were confirmed by FT-IR, ¹³C NMR, and ¹H NMR. The derivatives (0–100 µM) were evaluated for their inhibitory effect on tyrosinase activity using l-3,4-dihydroxyphenylalanine (l-DOPA) as substrate.

Results

All compounds showed inhibitory effects against the activity of the enzyme. About 23.72–55.08% inhibition was observed in the presence of 30 µM of each compound. The IC₅₀ values of the synthesized compounds were measured, and their inhibition properties were also visualized by zymography. Based on the results, the compounds 1a-e and 2a-e showed moderate inhibitory activities. Notably, pyrimidine derivatives 1a (IC₅₀=24.68) and 1d (IC₅₀=24.45) also exhibited similar inhibitory activities when compared with the positive control, kojic acid (IC₅₀=25.24 µM). Kinetic studies indicated that the type of inhibition was noncompetitive.

Conclusion

All results suggest that pyrimidine derivatives, especially 1d and 1a, can be considered as safe and efficient tyrosinase inhibitors.

Keywords:

• mushroom tyrosinase
• inhibitor
• pyrimidine derivatives
• noncompetitive inhibition

Acknowledgment

The authors thank the Research Council of the University of Guilan for the financial support of this study.

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.