Synlett
DOI: 10.1055/s-0043-1775489
letter
Small Molecules in Medicinal Chemistry

Design, Synthesis, Enzymatic Inhibition, and Antioxidant Activity of New 4-Phenylpiperazin-phenoxy-1,2,3-triazol-acetamide Derivatives as Tyrosinase Inhibitors

AmirHossein Alaeddini
a   School of Chemistry, College of Science, University of Tehran, Tehran, Iran
,
Somaye Karimian
b   Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Milad Noori
c   Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran, University of Science and Technology, Tehran, 16846-13114, Iran
,
Navid Dastyafteh
c   Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran, University of Science and Technology, Tehran, 16846-13114, Iran
,
Maryam Mohammadi-Khanaposhtani
d   Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
,
Minoo Khalili Ghomi
e   Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Morteza Bararjanian
e   Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Aida Iraji
f   Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
,
Shahrzad Javanshir
c   Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran, University of Science and Technology, Tehran, 16846-13114, Iran
,
Bagher Larijani
e   Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Parviz Rashidi Ranjbar  ∗
a   School of Chemistry, College of Science, University of Tehran, Tehran, Iran
,
Mohammad Mahdavi∗
e   Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Abstract

In this study, a 4-phenylpiperazin-phenoxy-1,2,3-triazol-acetamide scaffold was designed as a potent skeleton against tyrosinase by molecular hybridization theory. After that, nineteen derivatives of this scaffold were synthesized and evaluated in vitro and in silico against tyrosinase and the obtained data were compared with kojic acid as a strong tyrosinase inhibitor. Among the nineteen synthesized derivatives, four were more potent than kojic acid against mushroom tyrosinase. In this regard, one compound was around twofold more potent than kojic acid and was a competitive inhibitor for tyrosinase. In silico molecular modeling studies of the interactions of it and kojic acid with the active site of tyrosinase showed that this compound has more favorable binding energy than kojic acid. Moreover, a dynamics study of this compound showed that this compound forms a stable complex with tyrosinase.

Key words

1,2,3-triazole - 4-phenylpiperazine - tyrosinase - molecular modeling - dynamics

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0043-1775489.
  • Supporting Information


Publication History

Received: 18 January 2025

Accepted after revision: 10 April 2025

Article published online:
23 May 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
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