2. Academic Validation
  3. Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors

Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors

  • Sci Rep. 2025 Jan 4;15(1):846. doi: 10.1038/s41598-024-81328-8.
Sara Moghadam Farid 1,  Shahram Moradi Dehaghi 1,  Aida Iraji 2 3,  Mohammad Mahdavi 4 5,  Mina Saeedi 6 7
Affiliations

Affiliations

  • 1 Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran.
  • 2 Department of Persian Medicine, Research Center for Traditional Medicine and History of 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 Department of Persian Medicine, Research Center for Traditional Medicine and History of Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. momahdavi@sina.tums.ac.ir.
  • 5 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute (EMRI), Tehran University of Medical Sciences, Tehran, Iran. momahdavi@sina.tums.ac.ir.
  • 6 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 7 Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
PMID: 39755701 DOI: 10.1038/s41598-024-81328-8
Abstract

A series of novel phenylamino quinazolinone derivatives were designed and synthesized as potential Tyrosinase inhibitors. Among these compounds, 9r emerged as the most potent derivative, exhibiting IC50 values of 17.02 ± 1.66 µM, compared to kojic acid as the positive control with an IC50 value of 27.56 ± 1.27 µM. Antioxidant assessment of 9r compounds showed 24.67% inhibition at 100 µM. Molecular docking studies of these derivatives were conducted, revealing their proper fitting within the enzyme's active site. Additionally, density functional theory analysis was performed on the potent derivatives, indicating their stability and reactivity. Notably, the highest values of the energy gap were observed in 9r and 9s derivatives, underscoring their potential efficacy. Further kinetic studies of compound 9r, identified as the most potent derivative, demonstrated a competitive mode of inhibition with a Ki value of 14.87 µM. Molecular dynamics simulations of the 9r-tyrosinase complex revealed stability over time, with a reduction in critical residual fluctuation during the simulation. Overall, these findings contribute to a deeper understanding of the potential therapeutic value of these derivatives as Tyrosinase inhibitors.

Keywords

DFT; Molecular dynamics simulation; Phenylamino quinazolinone; Tyrosinase.

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