Evaluating the effects of disubstituted 3-hydroxy-1H-pyrrol-2(5H)-one analog as novel tyrosinase inhibitors

Naiemeh Alizadeh; Mohammad Hossein Sayahi; Aida Iraji; Rozita Yazzaf; Ali Moazzam; Koroush Mobaraki; Mehdi Adib; Mahshid Attarroshan; Bagher Larijani; Hossein Rastegar; Mehdi Khoshneviszadeh; Mohammad Mahdavi

doi:10.1016/j.bioorg.2022.105876

Evaluating the effects of disubstituted 3-hydroxy-1H-pyrrol-2(5H)-one analog as novel tyrosinase inhibitors

Bioorg Chem. 2022 Sep:126:105876. doi: 10.1016/j.bioorg.2022.105876. Epub 2022 May 16.

Authors

Affiliations

¹ School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.
² Department of Chemistry, Payam Noor University, Tehran, Iran.
³ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
⁶ Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁷ Cosmetic Products Research Center, Iranian Food and Drug Administration, MOHE, Tehran, Iran.
⁸ Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: Khoshnevim@sums.ac.ir.
⁹ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: momahdavi@sina.tums.ac.ir.

PMID: 35623142
DOI: 10.1016/j.bioorg.2022.105876

Abstract

In the present study, a series of 3-hydroxy-1H-pyrrol-2(5H)-one derivative were rationally designed and synthesized. The structure of targeted compounds was confirmed by IR, ¹H NMR, ¹³C NMR, and elemental analysis. Next, all derivatives were evaluated as tyrosinase inhibitors, and among the synthesized derivatives, compound 6a was proved to be the most potent inhibitor with an IC₅₀ value of 6.98 ± 1.05 µM. Kinetic study of compound 6a confirmed the mixed type of inhibitory activity towards tyrosinase. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase and exhibited interaction with important residues of the binding site.

Keywords: 3-hydroxy-1H-pyrrol-2(5H)-one; Molecular docking; Synthesis; Tyrosinase inhibitors.

MeSH terms

Agaricales*
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Molecular Docking Simulation
Molecular Structure
Monophenol Monooxygenase*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Monophenol Monooxygenase