新的硫代氨基甲酸类似物--合成、脲酶抑制、动力学和分子对接研究

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-05-03 DOI:10.1080/10426507.2024.2354727
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引用次数: 0

摘要

目前的研究报告介绍了通过两步化学转化合成硫代氨基甲酸盐(3-16)的过程。所有合成的衍生物都经过纯化,并通过质谱、核磁共振光谱(1H- 和 13C-NMR)和红外光谱进行了全面表征。除化合物 8 外,合成库中的所有成员都是新化合物。对合成的化合物库进行了筛选,以确定其对脲酶的抑制潜力。与用作标准的硫脲和乙酰羟肟酸(IC50 = 21.1 ± 0.2, 20.5 ± 0.4 µM)相比,几乎所有化合物都表现出了强大的活性,IC50 = 5.3 ± 0.8 - 15.5 ± 0.6 µM。而化合物 14 和 15 则表现出明显的活性,IC50 = 23.6 ± 0.6 和 27.3 ± 1.2 µM。此外,还进行了动力学研究以确定抑制模式,并采用分子对接来识别配体与酶的相互作用。因此,对接结果与体外结果方向一致。通过体外和硅学研究,化合物((E)-N-(2,5-二氯苯基)-2-(4-氟亚苄基)肼-1-硫代甲酰胺(3)和(E)-2-(2-氯亚苄基)-N-(2-氟苯基)肼硫代甲酰胺(5)被确定为最有效的脲酶抑制剂。
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New thiosemicarbazone analogues: synthesis, urease inhibition, kinetics and molecular docking studies

The current research reports the synthesis of a library of thiosemicarbazones (3-16) through a two-step chemical transformation. All the synthesized derivatives were purified and fully characterized through mass spectrometry, NMR spectroscopy (1H-, and 13C-NMR), and IR spectroscopy. All the members of the synthesized library were found to be new except compound 8. The synthesized library was screened for its inhibition potential against the urease enzyme. Almost all the compounds exhibited potent activity with the IC50 = 5.3 ± 0.8 − 15.5 ± 0.6 µM in comparison to the thiourea and acetohydroxamic acid used as standard (IC50 = 21.1 ± 0.2, 20.5 ± 0.4 µM). While significant activity was exhibited by compounds 14 and 15 with the IC50 = 23.6 ± 0.6 and 27.3 ± 1.2 µM. Furthermore, kinetic studies were carried out to determine the inhibition mode and molecular docking was employed to recognize the ligand-enzyme interactions. Thereby, the docking results are well in the direction of the in vitro results. Compounds ((E)-N-(2,5-dichlorophenyl)-2-(4-fluorobenzylidene)hydrazine-1-carbothioamide (3) and (E)-2-(2-chlorobenzylidene)-N-(2-fluorophenyl) hydrazinecarbothioamide (5) were identified as the most potent inhibitors of urease by both the in vitro and in silico studies.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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