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

AmirHossein Alaeddini; Somaye Karimian; Milad Noori; Navid Dastyafteh; Maryam Mohammadi-Khanaposhtani; Minoo Khalili Ghomi; Morteza Bararjanian; Aida Iraji; Shahrzad Javanshir; Bagher Larijani; Parviz Rashidi Ranjbar; Mohammad Mahdavi

doi:10.1055/s-0043-1775489

Synlett, Table of Contents

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

^aSchool of Chemistry, College of Science, University of Tehran, Tehran, Iran

,

Somaye Karimian

^bMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

,

Milad Noori

^cPharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran, University of Science and Technology, Tehran, 16846-13114, Iran

,

Navid Dastyafteh

^cPharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran, University of Science and Technology, Tehran, 16846-13114, Iran

,

Maryam Mohammadi-Khanaposhtani

^dCellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

,

Minoo Khalili Ghomi

^eEndocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

,

Morteza Bararjanian

^eEndocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

,

Aida Iraji

^fStem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran

,

Shahrzad Javanshir

^cPharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran, University of Science and Technology, Tehran, 16846-13114, Iran

,

Bagher Larijani

^eEndocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

,

Parviz Rashidi Ranjbar ∗

^aSchool of Chemistry, College of Science, University of Tehran, Tehran, Iran

,

Mohammad Mahdavi∗

^eEndocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

› Author Affiliations

Abstract

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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

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