{"title":"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","authors":"","doi":"10.1080/10426507.2024.2354727","DOIUrl":null,"url":null,"abstract":"<div><p>The current research reports the synthesis of a library of thiosemicarbazones (<strong>3-16</strong>) through a two-step chemical transformation. All the synthesized derivatives were purified and fully characterized through mass spectrometry, NMR spectroscopy (<sup>1</sup>H-, and <sup>13</sup>C-NMR), and IR spectroscopy. All the members of the synthesized library were found to be new except compound <strong>8</strong>. The synthesized library was screened for its inhibition potential against the urease enzyme. Almost all the compounds exhibited potent activity with the IC<sub>50</sub> = 5.3 ± 0.8 − 15.5 ± 0.6 µM in comparison to the thiourea and acetohydroxamic acid used as standard (IC<sub>50</sub> = 21.1 ± 0.2, 20.5 ± 0.4 µM). While significant activity was exhibited by compounds <strong>14</strong> and <strong>15</strong> with the IC<sub>50</sub> = 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 <em>in vitro</em> results. Compounds ((<em>E</em>)<em>-N</em>-(2,5-dichlorophenyl)-2-(4-fluorobenzylidene)hydrazine-1-carbothioamide (<strong>3</strong>) and (<em>E</em>)-2-(2-chlorobenzylidene)-<em>N</em>-(2-fluorophenyl) hydrazinecarbothioamide (<strong>5</strong>) were identified as the most potent inhibitors of urease by both the <em>in vitro</em> and <em>in silico</em> studies.</p></div>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New thiosemicarbazone analogues: synthesis, urease inhibition, kinetics and molecular docking studies\",\"authors\":\"\",\"doi\":\"10.1080/10426507.2024.2354727\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The current research reports the synthesis of a library of thiosemicarbazones (<strong>3-16</strong>) through a two-step chemical transformation. All the synthesized derivatives were purified and fully characterized through mass spectrometry, NMR spectroscopy (<sup>1</sup>H-, and <sup>13</sup>C-NMR), and IR spectroscopy. All the members of the synthesized library were found to be new except compound <strong>8</strong>. The synthesized library was screened for its inhibition potential against the urease enzyme. Almost all the compounds exhibited potent activity with the IC<sub>50</sub> = 5.3 ± 0.8 − 15.5 ± 0.6 µM in comparison to the thiourea and acetohydroxamic acid used as standard (IC<sub>50</sub> = 21.1 ± 0.2, 20.5 ± 0.4 µM). While significant activity was exhibited by compounds <strong>14</strong> and <strong>15</strong> with the IC<sub>50</sub> = 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 <em>in vitro</em> results. Compounds ((<em>E</em>)<em>-N</em>-(2,5-dichlorophenyl)-2-(4-fluorobenzylidene)hydrazine-1-carbothioamide (<strong>3</strong>) and (<em>E</em>)-2-(2-chlorobenzylidene)-<em>N</em>-(2-fluorophenyl) hydrazinecarbothioamide (<strong>5</strong>) were identified as the most potent inhibitors of urease by both the <em>in vitro</em> and <em>in silico</em> studies.</p></div>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-05-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/org/science/article/pii/S1042650724000194\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1042650724000194","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
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.
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.