Kaitlyn N Alcorn, Isabelle A Oberhauser, Matthew D Politeski, Todd J Eckroat
{"title":"n -烷基异黄酮和吲哚作为乙酰胆碱酯酶和丁基胆碱酯酶抑制剂的评价。","authors":"Kaitlyn N Alcorn, Isabelle A Oberhauser, Matthew D Politeski, Todd J Eckroat","doi":"10.1080/14756366.2023.2286935","DOIUrl":null,"url":null,"abstract":"<p><p>Two series of <i>N</i>-alkyl isatins and <i>N</i>-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the <i>N</i>-alkyl isatins <b>4a</b>-<b>j</b>, the addition of the <i>N</i>-alkyl group improved inhibition potency towards AChE and BChE compared to isatin. Selectivity towards inhibition of BChE was observed, and the increase in size of the <i>N</i>-alkyl group positively correlated to improved inhibition potency. The most potent inhibitor for BChE was <b>4i</b> (IC<sub>50</sub> = 3.77 µM, 22-fold selectivity for BChE over AChE). N-alkyl indoles <b>5a</b>-<b>j</b> showed similar inhibition of AChE, the most potent being <b>5g</b> (IC<sub>50</sub> = 35.0 µM), but <b>5a</b>-<b>j</b> lost activity towards BChE. This suggests an important role of the 3-oxo group on isatin for BChE inhibition, and molecular docking of <b>4i</b> with human BChE indicates a key hydrogen bond between this group and Ser198 and His438 of the BChE catalytic triad.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2286935"},"PeriodicalIF":5.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of <i>N</i>-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors.\",\"authors\":\"Kaitlyn N Alcorn, Isabelle A Oberhauser, Matthew D Politeski, Todd J Eckroat\",\"doi\":\"10.1080/14756366.2023.2286935\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Two series of <i>N</i>-alkyl isatins and <i>N</i>-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the <i>N</i>-alkyl isatins <b>4a</b>-<b>j</b>, the addition of the <i>N</i>-alkyl group improved inhibition potency towards AChE and BChE compared to isatin. Selectivity towards inhibition of BChE was observed, and the increase in size of the <i>N</i>-alkyl group positively correlated to improved inhibition potency. The most potent inhibitor for BChE was <b>4i</b> (IC<sub>50</sub> = 3.77 µM, 22-fold selectivity for BChE over AChE). N-alkyl indoles <b>5a</b>-<b>j</b> showed similar inhibition of AChE, the most potent being <b>5g</b> (IC<sub>50</sub> = 35.0 µM), but <b>5a</b>-<b>j</b> lost activity towards BChE. This suggests an important role of the 3-oxo group on isatin for BChE inhibition, and molecular docking of <b>4i</b> with human BChE indicates a key hydrogen bond between this group and Ser198 and His438 of the BChE catalytic triad.</p>\",\"PeriodicalId\":15769,\"journal\":{\"name\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"volume\":\"39 1\",\"pages\":\"2286935\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14756366.2023.2286935\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Enzyme Inhibition and Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14756366.2023.2286935","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors.
Two series of N-alkyl isatins and N-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the N-alkyl isatins 4a-j, the addition of the N-alkyl group improved inhibition potency towards AChE and BChE compared to isatin. Selectivity towards inhibition of BChE was observed, and the increase in size of the N-alkyl group positively correlated to improved inhibition potency. The most potent inhibitor for BChE was 4i (IC50 = 3.77 µM, 22-fold selectivity for BChE over AChE). N-alkyl indoles 5a-j showed similar inhibition of AChE, the most potent being 5g (IC50 = 35.0 µM), but 5a-j lost activity towards BChE. This suggests an important role of the 3-oxo group on isatin for BChE inhibition, and molecular docking of 4i with human BChE indicates a key hydrogen bond between this group and Ser198 and His438 of the BChE catalytic triad.
期刊介绍:
Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents.
Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research.
The journal’s focus includes current developments in:
Enzymology;
Cell biology;
Chemical biology;
Microbiology;
Physiology;
Pharmacology leading to drug design;
Molecular recognition processes;
Distribution and metabolism of biologically active compounds.