2. Academic Validation
  3. 2-(4-Fluorophenyl)-quinazolin-4(3H)-one as a novel tyrosinase inhibitor: Synthesis, inhibitory activity, and mechanism

2-(4-Fluorophenyl)-quinazolin-4(3H)-one as a novel tyrosinase inhibitor: Synthesis, inhibitory activity, and mechanism

  • Bioorg Med Chem. 2016 Oct 1;24(19):4620-4625. doi: 10.1016/j.bmc.2016.07.068.
Rui Wang 1,  Wei-Ming Chai 2,  Qin Yang 3,  Man-Kun Wei 1,  Yiyuan Peng 4
Affiliations

Affiliations

  • 1 Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
  • 2 Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Nanchang, Jiangxi 330022, China. Electronic address: chaiweiming@jxnu.edu.cn.
  • 3 Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Nanchang, Jiangxi 330022, China.
  • 4 Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Nanchang, Jiangxi 330022, China. Electronic address: yiyuanpeng@jxnu.edu.cn.
PMID: 27527415 DOI: 10.1016/j.bmc.2016.07.068
Abstract

2-(4-Fluorophenyl)-quinazolin-4(3H)-one (FQ) was synthesized, and its structure was identified with (1)H nuclear magnetic resonance ((1)H NMR), (13)C nuclear magnetic resonance ((13)C NMR), fourier transform infrared spectroscopy (FTIR), and high resolution mass spectrometry (HRMS). From the Enzyme analysis, the results showed that it could inhibit the diphenolase activity of Tyrosinase (IC50=120±2μM). Furthermore, the results of kinetic studies showed that the compound was a reversible mixed-type inhibitor, and that the inhibition constants were determined to be 703.2 (KI) and 222.1μM (KIS). The results of fluorescence quenching experiment showed that the compound could interact with Tyrosinase and the substrates (tyrosine and l-DOPA). Molecular docking analysis revealed that the mass transfer rate was affected by FQ blocking the Enzyme catalytic center. In brief, current study identified a novel Tyrosinase Inhibitor which deserved further study for hyperpigmentation drugs.

Keywords

Fluorescence; Molecular docking; Quinazolinone; Synthesis; Tyrosinase inhibitor.

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