Investigation of the interaction between benzaldehyde thiosemicarbazone compounds and xanthine oxidase
Investigation of the interaction between benzaldehyde thiosemicarbazone compounds and xanthine oxidase
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DOI：
10.1016/j.molstruc.2018.01.020
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发表时间：
2018-05-05
影响因子：
3.8
通讯作者：
Cao, Shuwen
中科院分区：
文献类型：
--
作者：
Li, Mengrong;Yu, Yanying;Cao, Shuwen
合成了一系列取代苯甲醛缩氨基硫脲类化合物(1-7)作为黄嘌呤氧化酶(XO)的抑制剂，并用紫外光谱、荧光光谱和分子对接等方法研究了取代苯甲醛缩氨基硫脲类化合物(1-7)与XO的相互作用。结果表明，取代苯甲醛缩氨基硫脲类化合物与XO的相互作用主要以氢键和疏水性为主，在化合物4的苯环对位引入-OH，在氨基末端引入Ph-或Me-基团，提高了修饰剂的抑制活性。结果表明，新引入的苯环通过与芳香族氨基酸残基(如Phe残基)之间的pi-pi堆积力与XO的疏水空腔相互作用，从而大大提高了修饰剂的抑制活性。我们认为在化合物4的氨基末端引入Ph基团，在苯环的对位引入-OH基团是获得新型XO抑制剂的一条很好的途径。8-苯胺基-1-萘磺酸荧光探针辅助荧光光谱和分子对接有助于初步了解目标化合物与XO之间的相互作用，值得进一步研究。(C)2018爱思唯尔B.V.保留所有权利。
A series of substituted benzaldehyde thiosemicarbazide compounds (1-7) were synthesized as xanthine oxidase (XO) inhibitors, and the interactions between substituted benzaldehyde thiosemicarbazide compounds (1-7) and XO were studied by ultraviolet spectroscopy, fluorescence spectroscopy, and molecular docking. It was found that the hydrogen bond and hydrophobicity were the main interactions between substituted benzaldehyde thiosemicarbazide compounds and XO, and introducing -OH at the para position of the benzene ring and a Ph- or Me-group at the amino terminal of compound 4 increased the modifier's inhibitory activity. The results suggest that the newly introduced benzene ring interacted with the hydrophobic cavity of XO by means of the pi-pi stacking force between the newly introduced benzene ring and the aromatic amino acid residues, such as the Phe residue, which greatly increased the modifier's inhibitory activity. We conclude that introducing the Ph-group at the amino terminal of compound 4 and the -OH group at the para position of the benzene ring was a good route to obtain novel XO inhibitors. Fluorescence spectroscopy assisted by 8-anilino-1-naphthalenesulfonic acid fluorescence probing and molecular docking were helpful for achieving a preliminary and relatively clear understanding of the interactions between target compounds and XO, which deserve further study. (C) 2018 Elsevier B.V. All rights reserved.