2. Academic Validation
  3. Structure-based development of 3,5-dihydroxybenzoyl-hydrazineylidene as tyrosinase inhibitor; in vitro and in silico study

Structure-based development of 3,5-dihydroxybenzoyl-hydrazineylidene as tyrosinase inhibitor; in vitro and in silico study

  • Sci Rep. 2024 Jan 17;14(1):1540. doi: 10.1038/s41598-024-52022-6.
Azzam Bagheri 1,  Shahram Moradi 1,  Aida Iraji 2 3 4,  Mohammad Mahdavi 5
Affiliations

Affiliations

  • 1 Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Tehran, Iran.
  • 2 Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. iraji@sums.ac.ir.
  • 3 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. iraji@sums.ac.ir.
  • 4 Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran. iraji@sums.ac.ir.
  • 5 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. momahdavi@sina.tums.ac.ir.
PMID: 38233558 DOI: 10.1038/s41598-024-52022-6
Abstract

A series of new analogs of 3,5-dihydroxybenzoyl-hydrazineylidene conjugated to different methoxyphenyl triazole (11a-n) synthesized using click reaction. The structures of all synthesized compounds were characterized by FTIR, 1H, 13C-NMR spectroscopy, and CHO analysis. The Tyrosinase inhibitory potential of the synthesized compounds was studied. The newly synthesized scaffolds were found to illustrate the variable degree of the inhibitory profile, and the most potent analog of this series was that one bearing 4-methoxyphenyl moiety, and exhibited an IC50 value of 55.39 ± 4.93 µM. The kinetic study of the most potent derivative reveals a competitive mode of inhibition. Next, molecular docking studies were performed to understand the potent inhibitor's binding mode within the enzyme's binding site. Molecular dynamics simulations were accomplished to further investigate the orientation and binding interaction over time and the stability of the 11m-tyrosinase complex.

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