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

Authors Mirmortazavi SS, Farvandi M, Ghafouri H, Mohammadi A, Shourian M

Received 19 March 2019

Accepted for publication 31 May 2019

Published 8 July 2019 Volume 2019:13 Pages 2169—2178

DOI https://doi.org/10.2147/DDDT.S209324

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


S Shohreh Mirmortazavi,1 Mahdieh Farvandi,1 Hossein Ghafouri,1 Asadollah Mohammadi,2 Mostafa Shourian1

1Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran; 2Department of Chemistry, Faculty of Sciences, University of Guilan, Rasht, Iran

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, 13,C NMR, and 1,H 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

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