苯并恶唑基噻唑杂化类似物:合成、体外胆碱酯酶抑制及分子对接研究

IF 3.1 Q2 TOXICOLOGY
Rafaqat Hussain , Fazal Rahim , Wajid Rehman , Syed Adnan Ali Shah , Shoaib Khan , Imran Khan , Liaqat Rasheed , Syahrul Imran , Abdul Wadood , Magda H. Abdellatif
{"title":"苯并恶唑基噻唑杂化类似物:合成、体外胆碱酯酶抑制及分子对接研究","authors":"Rafaqat Hussain ,&nbsp;Fazal Rahim ,&nbsp;Wajid Rehman ,&nbsp;Syed Adnan Ali Shah ,&nbsp;Shoaib Khan ,&nbsp;Imran Khan ,&nbsp;Liaqat Rasheed ,&nbsp;Syahrul Imran ,&nbsp;Abdul Wadood ,&nbsp;Magda H. Abdellatif","doi":"10.1016/j.comtox.2022.100253","DOIUrl":null,"url":null,"abstract":"<div><p>Acetylcholinesterase and butyrylcholinesterase enzymes are therapeutic target for Alzheimer disease and their inhibitors play a vital role for the treatment of this disease. <strong>A</strong> new series of benzoxazole based 1,3-thiazole hybrid scaffolds (<strong>1</strong>–<strong>20</strong>) were synthesized and assessed for acetylcholinesterase and butyrylcholinesterase inhibition profile and then characterized by using different spectroscopic tools such as <sup>1</sup>H NMR, <sup>13</sup>C NMR and HREI-MS spectroscopy. Four scaffolds such as <strong>1</strong>, <strong>4</strong>, <strong>12</strong> and <strong>19</strong> showed AChE potency almost comparable to standard drug having IC<sub>50</sub> values 0.692 ± 0.087, 0.947 ± 0.089, 0.38 ± 0.016 and 0.742 ± 0.042 µM, while nine scaffolds such as <strong>1</strong>, <strong>4</strong>, <strong>6</strong>, <strong>8</strong>, <strong>9</strong>, <strong>12</strong>, <strong>13</strong>, <strong>14</strong> and <strong>19</strong> showed superior BuChE potency than standard drug having IC<sub>50</sub> values 2.54 ± 0.10, 1.79 ± 0.20, 3.25 ± 0.18, 2.48 ± 0.05, 1.33 ± 0.05, 2.19 ± 0.08, 2.81 ± 0.20, 2.23 ± 0.10 and 2.10 ± 0.05 µM respectively. Nonetheless, remaining analogs were found to have moderate activity. Among the synthesized series, analogs <strong>12</strong> (IC<sub>50</sub> <strong>=</strong> 0.38 ± 0.016 µM) and <strong>9</strong> (IC<sub>50</sub> <strong>=</strong> 1.33 ± 0.05 µM) were identified as the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes. In addition, the molecular docking studies were carried out to find out the possible binding mode of interactions of most active analogs with enzymes active site and results supported the experimental data.</p></div>","PeriodicalId":37651,"journal":{"name":"Computational Toxicology","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Benzoxazole based thiazole hybrid analogs: Synthesis, in vitro cholinesterase inhibition, and molecular docking studies\",\"authors\":\"Rafaqat Hussain ,&nbsp;Fazal Rahim ,&nbsp;Wajid Rehman ,&nbsp;Syed Adnan Ali Shah ,&nbsp;Shoaib Khan ,&nbsp;Imran Khan ,&nbsp;Liaqat Rasheed ,&nbsp;Syahrul Imran ,&nbsp;Abdul Wadood ,&nbsp;Magda H. Abdellatif\",\"doi\":\"10.1016/j.comtox.2022.100253\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Acetylcholinesterase and butyrylcholinesterase enzymes are therapeutic target for Alzheimer disease and their inhibitors play a vital role for the treatment of this disease. <strong>A</strong> new series of benzoxazole based 1,3-thiazole hybrid scaffolds (<strong>1</strong>–<strong>20</strong>) were synthesized and assessed for acetylcholinesterase and butyrylcholinesterase inhibition profile and then characterized by using different spectroscopic tools such as <sup>1</sup>H NMR, <sup>13</sup>C NMR and HREI-MS spectroscopy. Four scaffolds such as <strong>1</strong>, <strong>4</strong>, <strong>12</strong> and <strong>19</strong> showed AChE potency almost comparable to standard drug having IC<sub>50</sub> values 0.692 ± 0.087, 0.947 ± 0.089, 0.38 ± 0.016 and 0.742 ± 0.042 µM, while nine scaffolds such as <strong>1</strong>, <strong>4</strong>, <strong>6</strong>, <strong>8</strong>, <strong>9</strong>, <strong>12</strong>, <strong>13</strong>, <strong>14</strong> and <strong>19</strong> showed superior BuChE potency than standard drug having IC<sub>50</sub> values 2.54 ± 0.10, 1.79 ± 0.20, 3.25 ± 0.18, 2.48 ± 0.05, 1.33 ± 0.05, 2.19 ± 0.08, 2.81 ± 0.20, 2.23 ± 0.10 and 2.10 ± 0.05 µM respectively. Nonetheless, remaining analogs were found to have moderate activity. Among the synthesized series, analogs <strong>12</strong> (IC<sub>50</sub> <strong>=</strong> 0.38 ± 0.016 µM) and <strong>9</strong> (IC<sub>50</sub> <strong>=</strong> 1.33 ± 0.05 µM) were identified as the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes. In addition, the molecular docking studies were carried out to find out the possible binding mode of interactions of most active analogs with enzymes active site and results supported the experimental data.</p></div>\",\"PeriodicalId\":37651,\"journal\":{\"name\":\"Computational Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Computational Toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S246811132200041X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computational Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S246811132200041X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 4

摘要

乙酰胆碱酯酶和丁基胆碱酯酶是阿尔茨海默病的治疗靶点,其抑制剂在阿尔茨海默病的治疗中起着至关重要的作用。合成了一系列新的以苯并恶唑为基础的1,3-噻唑杂化支架(1 - 20),对其乙酰胆碱酯酶和丁基胆碱酯酶的抑制性能进行了评价,并利用1H NMR、13C NMR和HREI-MS等不同的波谱工具对其进行了表征。四个支架,如1、4、12和19显示疼痛效果几乎与标准药物IC50值0.692±0.087,0.947±0.089,0.38±0.016,0.742±0.042µM,而九个支架,如1,4,6,8,9日,12日,13日,14日和19显示优越的大餐比标准药物效力IC50值2.54±0.10,1.79±0.20,3.25±0.18,2.48±0.05,1.33±0.05,2.19±0.08,2.81±0.20,2.23±0.10,2.10±0.05µM分别。尽管如此,剩下的类似物被发现有适度的活性。在所合成的系列化合物中,类似物12 (IC50 = 0.38±0.016µM)和9 (IC50 = 1.33±0.05µM)是乙酰胆碱酯酶和丁基胆碱酯酶最有效的抑制剂。此外,我们还进行了分子对接研究,找出了大多数活性类似物与酶活性位点的相互作用可能的结合方式,结果支持了实验数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Benzoxazole based thiazole hybrid analogs: Synthesis, in vitro cholinesterase inhibition, and molecular docking studies

Acetylcholinesterase and butyrylcholinesterase enzymes are therapeutic target for Alzheimer disease and their inhibitors play a vital role for the treatment of this disease. A new series of benzoxazole based 1,3-thiazole hybrid scaffolds (120) were synthesized and assessed for acetylcholinesterase and butyrylcholinesterase inhibition profile and then characterized by using different spectroscopic tools such as 1H NMR, 13C NMR and HREI-MS spectroscopy. Four scaffolds such as 1, 4, 12 and 19 showed AChE potency almost comparable to standard drug having IC50 values 0.692 ± 0.087, 0.947 ± 0.089, 0.38 ± 0.016 and 0.742 ± 0.042 µM, while nine scaffolds such as 1, 4, 6, 8, 9, 12, 13, 14 and 19 showed superior BuChE potency than standard drug having IC50 values 2.54 ± 0.10, 1.79 ± 0.20, 3.25 ± 0.18, 2.48 ± 0.05, 1.33 ± 0.05, 2.19 ± 0.08, 2.81 ± 0.20, 2.23 ± 0.10 and 2.10 ± 0.05 µM respectively. Nonetheless, remaining analogs were found to have moderate activity. Among the synthesized series, analogs 12 (IC50 = 0.38 ± 0.016 µM) and 9 (IC50 = 1.33 ± 0.05 µM) were identified as the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes. In addition, the molecular docking studies were carried out to find out the possible binding mode of interactions of most active analogs with enzymes active site and results supported the experimental data.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Computational Toxicology
Computational Toxicology Computer Science-Computer Science Applications
CiteScore
5.50
自引率
0.00%
发文量
53
审稿时长
56 days
期刊介绍: Computational Toxicology is an international journal publishing computational approaches that assist in the toxicological evaluation of new and existing chemical substances assisting in their safety assessment. -All effects relating to human health and environmental toxicity and fate -Prediction of toxicity, metabolism, fate and physico-chemical properties -The development of models from read-across, (Q)SARs, PBPK, QIVIVE, Multi-Scale Models -Big Data in toxicology: integration, management, analysis -Implementation of models through AOPs, IATA, TTC -Regulatory acceptance of models: evaluation, verification and validation -From metals, to small organic molecules to nanoparticles -Pharmaceuticals, pesticides, foods, cosmetics, fine chemicals -Bringing together the views of industry, regulators, academia, NGOs
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信