Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis,Inhibitory Activity,and Mechanism |
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| Authors: | Yaru Huang Jiefang Yang Yunyang Chi Chun Gong Haikuan Yang Fanxin Zeng Fang Gao Xiaoju Hua Zongde Wang |
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| Affiliation: | 1.East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration, College of Forestry, Jiangxi Agricultural University, Nanchang 330045, China;2.Jiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, China;3.Yongfeng County Natural Resources Bureau, Ji’an 331500, China |
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| Abstract: | We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 μM (IC50 = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the KI and KIS inhibition constants to be 117.07 μM and 423.63 μM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug. |
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| Keywords: | tyrosinase inhibitor citral derivatives fluorescence quenching molecular docking |
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