{"title":"新型三氟甲基苯甲酰胺作为有前途的 CETP 抑制剂的合成、分子建模和生物学评价。","authors":"Reema Abu Khalaf, Amani Abusaad, Bara'a Al-Nawaiseh, Dima Sabbah, Ghadeer Albadawi","doi":"10.2174/1573409919666230509123852","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis.</p><p><strong>Objective: </strong>Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels.</p><p><strong>Methods: </strong>Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed.</p><p><strong>Results: </strong><i>In vitro</i> biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC<sub>50</sub> of 1.03 μM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation.</p><p><strong>Conclusion: </strong>Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors.\",\"authors\":\"Reema Abu Khalaf, Amani Abusaad, Bara'a Al-Nawaiseh, Dima Sabbah, Ghadeer Albadawi\",\"doi\":\"10.2174/1573409919666230509123852\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis.</p><p><strong>Objective: </strong>Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels.</p><p><strong>Methods: </strong>Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed.</p><p><strong>Results: </strong><i>In vitro</i> biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC<sub>50</sub> of 1.03 μM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation.</p><p><strong>Conclusion: </strong>Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.</p>\",\"PeriodicalId\":10886,\"journal\":{\"name\":\"Current computer-aided drug design\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current computer-aided drug design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1573409919666230509123852\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current computer-aided drug design","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1573409919666230509123852","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors.
Background: Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis.
Objective: Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels.
Methods: Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed.
Results: In vitro biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC50 of 1.03 μM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation.
Conclusion: Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.
期刊介绍：
Aims & Scope
Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design.
Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.
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