title: 2-(4-Fluorophenyl)-quinazolin-4(3H)-one as a novel tyrosinase inhibitor: Synthesis, inhibitory activity, and mechanism.
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.
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chai
authors.affiliation: 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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
authors.forename: Man-Kun
authors.initials: MK
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Peng
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D054879:Halogenation; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052999:Quinazolinones / Q000737:chemistry* / Q000494:pharmacology*; D013302:Streptomyces / Q000201:enzymology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D052999:Quinazolinones; D014443:Tyrosine; D007980:Levodopa; C061339:4-hydroxyquinazoline; D014442:Monophenol Monooxygenase
keywords: Fluorescence; Molecular docking; Quinazolinone; Synthesis; Tyrosinase inhibitor