{"title":"作为拟抗 CETP 药物的正氟化苯磺酰胺的合成和室内研究","authors":"Reema Abu Khalaf, Lama Jaradat, Maha Habash","doi":"10.2174/0113852728295939240315040152","DOIUrl":null,"url":null,"abstract":": Cardiovascular disease is one of the primary causes of death. Atherosclerosis produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl Ester Transfer Protein (CETP) is a protein that aids in reverse cholesterol transport. It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol. In this study, ten ortho-fluoro substituted benzenesulfonamides 6a-6j were prepared, and their structure was fully determined using 1H NMR, 13C NMR, HR-MS, and IR. In vitro biological evaluation showed that compound 6d has the highest inhibitory activity with 100% inhibition, while compounds 6a-6c and 6e-6j had activities ranged from 29% - 83% at 10 μM concentration. Interestingly, para-substituted derivatives (6d, 6g, and 6j) were observed to have greater CETP inhibitory activities than their ortho- and meta- analogues irrespective to the nature of substituent, i.e., CH3, Cl, or NO2. Ligandfit docking experiment revealed the difference in the binding mode among the synthesized compounds, which is reflected in their CETP inhibitory activity. background: Cardiovascular disease is one of the primary causes of death. Atherosclerosis produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl ester transfer protein (CETP) is a protein that aids in reverse cholesterol transport. It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol. method: and their structure was fully determined using 1H-NMR, 13C-NMR, HR-MS, and IR. conclusion: Ligandfit docking experiment revealed the difference in the binding mode among the synthesized compounds which is reflected on their CETP inhibitory activity.","PeriodicalId":10926,"journal":{"name":"Current Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and In-Silico Studies of Ortho-Fluorinated Benzenesulfonamides as Putative Anti-CETP Agents\",\"authors\":\"Reema Abu Khalaf, Lama Jaradat, Maha Habash\",\"doi\":\"10.2174/0113852728295939240315040152\",\"DOIUrl\":null,\"url\":null,\"abstract\":\": Cardiovascular disease is one of the primary causes of death. Atherosclerosis produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl Ester Transfer Protein (CETP) is a protein that aids in reverse cholesterol transport. It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol. In this study, ten ortho-fluoro substituted benzenesulfonamides 6a-6j were prepared, and their structure was fully determined using 1H NMR, 13C NMR, HR-MS, and IR. In vitro biological evaluation showed that compound 6d has the highest inhibitory activity with 100% inhibition, while compounds 6a-6c and 6e-6j had activities ranged from 29% - 83% at 10 μM concentration. Interestingly, para-substituted derivatives (6d, 6g, and 6j) were observed to have greater CETP inhibitory activities than their ortho- and meta- analogues irrespective to the nature of substituent, i.e., CH3, Cl, or NO2. Ligandfit docking experiment revealed the difference in the binding mode among the synthesized compounds, which is reflected in their CETP inhibitory activity. background: Cardiovascular disease is one of the primary causes of death. Atherosclerosis produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl ester transfer protein (CETP) is a protein that aids in reverse cholesterol transport. It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol. method: and their structure was fully determined using 1H-NMR, 13C-NMR, HR-MS, and IR. conclusion: Ligandfit docking experiment revealed the difference in the binding mode among the synthesized compounds which is reflected on their CETP inhibitory activity.\",\"PeriodicalId\":10926,\"journal\":{\"name\":\"Current Organic Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Organic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.2174/0113852728295939240315040152\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Organic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.2174/0113852728295939240315040152","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Synthesis and In-Silico Studies of Ortho-Fluorinated Benzenesulfonamides as Putative Anti-CETP Agents
: Cardiovascular disease is one of the primary causes of death. Atherosclerosis produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl Ester Transfer Protein (CETP) is a protein that aids in reverse cholesterol transport. It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol. In this study, ten ortho-fluoro substituted benzenesulfonamides 6a-6j were prepared, and their structure was fully determined using 1H NMR, 13C NMR, HR-MS, and IR. In vitro biological evaluation showed that compound 6d has the highest inhibitory activity with 100% inhibition, while compounds 6a-6c and 6e-6j had activities ranged from 29% - 83% at 10 μM concentration. Interestingly, para-substituted derivatives (6d, 6g, and 6j) were observed to have greater CETP inhibitory activities than their ortho- and meta- analogues irrespective to the nature of substituent, i.e., CH3, Cl, or NO2. Ligandfit docking experiment revealed the difference in the binding mode among the synthesized compounds, which is reflected in their CETP inhibitory activity. background: Cardiovascular disease is one of the primary causes of death. Atherosclerosis produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl ester transfer protein (CETP) is a protein that aids in reverse cholesterol transport. It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol. method: and their structure was fully determined using 1H-NMR, 13C-NMR, HR-MS, and IR. conclusion: Ligandfit docking experiment revealed the difference in the binding mode among the synthesized compounds which is reflected on their CETP inhibitory activity.
期刊介绍:
Current Organic Chemistry aims to provide in-depth/mini reviews on the current progress in various fields related to organic chemistry including bioorganic chemistry, organo-metallic chemistry, asymmetric synthesis, heterocyclic chemistry, natural product chemistry, catalytic and green chemistry, suitable aspects of medicinal chemistry and polymer chemistry, as well as analytical methods in organic chemistry. The frontier reviews provide the current state of knowledge in these fields and are written by chosen experts who are internationally known for their eminent research contributions. The Journal also accepts high quality research papers focusing on hot topics, highlights and letters besides thematic issues in these fields. Current Organic Chemistry should prove to be of great interest to organic chemists in academia and industry, who wish to keep abreast with recent developments in key fields of organic chemistry.