新型喹唑啉酮衍生物作为新型酪氨酸酶抑制剂的设计、抑制活性及机制。
Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism.
机构信息
East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration, College of Forestry, Jiangxi Agricultural University, Nanchang 330045, China.
Jiangxi Academy of Forestry, Camphor Engineering Research Center of National Forestry and Grassland Administration, Nanchang 330032, China.
出版信息
Molecules. 2022 Aug 29;27(17):5558. doi: 10.3390/molecules27175558.
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(3)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 μM (IC = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the K and K 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.
我们合成了一系列喹唑啉酮衍生物作为酪氨酸酶抑制剂，并评估了它们的抑制常数。我们从天然柠檬醛合成了 2-(2,6-二甲基庚-1,5-二烯-1-基)喹唑啉-4(3)-酮 (Q1)。导致 Q1 活性损失 50%的浓度为 103 ± 2 μM (IC = 103 ± 2 μM)。此外，我们认为 Q1 是一种混合型和可逆的酪氨酸酶抑制剂，并确定了 K 和 K 抑制常数分别为 117.07 μM 和 423.63 μM。我们的荧光实验表明，Q1 除了与酪氨酸和 L-DOPA 与酪氨酸酶相互作用外，还可以与酪氨酸和 L-DOPA 的底物相互作用。分子对接研究表明，Q1 与酪氨酸酶的结合是由氢键和疏水性驱动的。简而言之，本研究证实了一种新的酪氨酸酶抑制剂，有望开发成一种新型的色素沉着药物。
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