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

Publication date: 1 October 2016
Source:Bioorganic & Medicinal Chemistry, Volume 24, Issue 19
Author(s): Rui Wang, Wei-Ming Chai, Qin Yang, Man-Kun Wei, Yiyuan Peng
2-(4-Fluorophenyl)-quinazolin-4(3H)-one (FQ) was synthesized, and its structure was identified with ¹H nuclear magnetic resonance (¹H NMR), ¹³C nuclear magnetic resonance (¹³C 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.

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