Journal of the Iranian Chemical Society, ( ISI ), Year (2021-9)

Title : ( Introducing a potential lead structure for the synthesis of more specific inhibitors of tyrosinases and catechol oxidases )

Authors: faheimeh haghbeen , Nargess Ghorbanian , Golnaz Hajatpour , Javad Zamani Amirzakaria , Hossein Eshghi , Kamahldin Haghbeen ,

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Abstract

Based on tyrosinase inhibition science, two pyrimidine derivatives were designed and studied. Docking of 2-dibenzylamine-5-hydroxy pyrimidine (dba5HP) and 2-benzylamino-5-hydroxy pyrimidine (ba5HP) on mushroom tyrosinase (MT) showed that the former could not occupy MT active site pocket, while ba5HP could do so (Moldock score = − 63.95). MD simulation revealed that the complex of ba5HP-MT reached stability < 30 ns. In silico biocompatibility examinations predicted high permeability, good bioavailability, low toxicity, and synthetic accessibility of 1.59 for ba5HP with high probability for CYP-mediated metabolism. Subsequently, both compounds were synthesized in good yields. Kinetics studies proved that, unlike dba5HP, ba5HP could strongly inhibit MT competitively (IC50 = 32.28, Ki = 11.32 μM). Considering the facile synthesis, potential for structural modifications, and passing most of the lead-likeness filters, it seems likely that ba5HP plays key roles in the syntheses of novel depigmentation medicines as well as more specific inhibitors for various tyrosinases and polyphenol oxidases.

Keywords

, 2, Amino, 5, hydroxy pyrimidine · Antibrowning · Depigmentation · Lead compound · Pharmacokinetic
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@article{paperid:1086453,
author = {Haghbeen, Faheimeh and Nargess Ghorbanian and Golnaz Hajatpour and Javad Zamani Amirzakaria and Eshghi, Hossein and Kamahldin Haghbeen},
title = {Introducing a potential lead structure for the synthesis of more specific inhibitors of tyrosinases and catechol oxidases},
journal = {Journal of the Iranian Chemical Society},
year = {2021},
month = {September},
issn = {1735-207X},
keywords = {2-Amino-5-hydroxy pyrimidine · Antibrowning · Depigmentation · Lead compound · Pharmacokinetic},
}

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%0 Journal Article
%T Introducing a potential lead structure for the synthesis of more specific inhibitors of tyrosinases and catechol oxidases
%A Haghbeen, Faheimeh
%A Nargess Ghorbanian
%A Golnaz Hajatpour
%A Javad Zamani Amirzakaria
%A Eshghi, Hossein
%A Kamahldin Haghbeen
%J Journal of the Iranian Chemical Society
%@ 1735-207X
%D 2021

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