从 Fritillaria cirrhosa D.Don (Liliaceae, syn. Fritillaria roylei Hook) 中以生物化学计量学为指导分离出新的异甾体生物碱作为乙酰胆碱酯酶抑制剂。

IF 2.5 3区 医学 Q3 CHEMISTRY, MEDICINAL
Prateek Singh Bora, Shivani Puri, Prithvi Pal Singh, Upendra Sharma
{"title":"从 Fritillaria cirrhosa D.Don (Liliaceae, syn. Fritillaria roylei Hook) 中以生物化学计量学为指导分离出新的异甾体生物碱作为乙酰胆碱酯酶抑制剂。","authors":"Prateek Singh Bora, Shivani Puri, Prithvi Pal Singh, Upendra Sharma","doi":"10.1016/j.fitote.2024.106279","DOIUrl":null,"url":null,"abstract":"<p><p>Globally, Alzheimer's disease is an urgent public health concern with the ageing population in developing nations. Recent studies have identified isosteroidal alkaloids as promising therapeutic agents for Alzheimer's treatment. Fritillaria species are well-known rich sources of steroidal and isosteroidal alkaloids. In this context, the current study focuses on the biochemometric-guided isolation of three previously undescribed and two known isosteroidal alkaloids as acetylcholinesterase (AChE) inhibitors from the bulbs of Fritillaria cirrhosa D.Don. The isolated molecules were characterized by NMR, HR-ESI-MS, FT-IR, and DP4+ analysis. Subsequently, all isolates were evaluated for AChE inhibitory activity using Ellman's method. Among the evaluated molecules, 1 (IC<sub>50</sub>: 33.0 ± 4.4 μM) and 5 (IC<sub>50</sub>: 24.7 ± 4.5 μM) showed promising AChE inhibition in vitro. Enzyme kinetic studies of isolated molecules revealed mixed inhibition kinetics with K<sub>i</sub> varying from 1.3 to 24.4 μM. Moreover, the in silico studies showed excellent binding affinities of isolated molecules with the target protein and good drug-like ADMET properties. The present study identified new isosteroidal alkaloids as promising AChE inhibitors from F. cirrhosa bulbs via a biochemometric approach and advocated their further exploration for treating neurodegenerative disorders.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biochemometric-guided isolation of new Isosteroidal alkaloids from Fritillaria cirrhosa D.Don (Liliaceae, syn. Fritillaria roylei Hook) as acetylcholinesterase inhibitors.\",\"authors\":\"Prateek Singh Bora, Shivani Puri, Prithvi Pal Singh, Upendra Sharma\",\"doi\":\"10.1016/j.fitote.2024.106279\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Globally, Alzheimer's disease is an urgent public health concern with the ageing population in developing nations. Recent studies have identified isosteroidal alkaloids as promising therapeutic agents for Alzheimer's treatment. Fritillaria species are well-known rich sources of steroidal and isosteroidal alkaloids. In this context, the current study focuses on the biochemometric-guided isolation of three previously undescribed and two known isosteroidal alkaloids as acetylcholinesterase (AChE) inhibitors from the bulbs of Fritillaria cirrhosa D.Don. The isolated molecules were characterized by NMR, HR-ESI-MS, FT-IR, and DP4+ analysis. Subsequently, all isolates were evaluated for AChE inhibitory activity using Ellman's method. Among the evaluated molecules, 1 (IC<sub>50</sub>: 33.0 ± 4.4 μM) and 5 (IC<sub>50</sub>: 24.7 ± 4.5 μM) showed promising AChE inhibition in vitro. Enzyme kinetic studies of isolated molecules revealed mixed inhibition kinetics with K<sub>i</sub> varying from 1.3 to 24.4 μM. Moreover, the in silico studies showed excellent binding affinities of isolated molecules with the target protein and good drug-like ADMET properties. The present study identified new isosteroidal alkaloids as promising AChE inhibitors from F. cirrhosa bulbs via a biochemometric approach and advocated their further exploration for treating neurodegenerative disorders.</p>\",\"PeriodicalId\":12147,\"journal\":{\"name\":\"Fitoterapia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fitoterapia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.fitote.2024.106279\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fitoterapia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.fitote.2024.106279","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

摘要

在全球范围内,随着发展中国家人口的老龄化,阿尔茨海默氏症已成为一个紧迫的公共卫生问题。最近的研究发现,异甾体生物碱是治疗老年痴呆症的有前途的药物。众所周知,鱼腥草物种富含类固醇和异类固醇生物碱。在此背景下,本研究侧重于在生物化学计量学的指导下,从 Fritillaria cirrhosa D.Don 的鳞茎中分离出三种以前未曾描述过的异甾体生物碱和两种已知的异甾体生物碱,作为乙酰胆碱酯酶(AChE)抑制剂。分离出的分子通过核磁共振、HR-ESI-MS、傅立叶变换红外光谱和 DP4+ 分析进行了表征。随后,采用埃尔曼法评估了所有分离物的 AChE 抑制活性。在评估的分子中,1(IC50:33.0 ± 4.4 μM)和 5(IC50:24.7 ± 4.5 μM)在体外显示出良好的 AChE 抑制作用。对分离的分子进行的酶动力学研究显示了混合抑制动力学,Ki 从 1.3 μM 到 24.4 μM 不等。此外,硅学研究表明,分离出的分子与靶蛋白有极好的结合亲和力,并具有良好的类药物 ADMET 特性。本研究通过生物化学计量学方法从 F. cirrhosa 鳞茎中发现了新的异甾体生物碱作为有前景的 AChE 抑制剂,并主张进一步探索其在治疗神经退行性疾病方面的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biochemometric-guided isolation of new Isosteroidal alkaloids from Fritillaria cirrhosa D.Don (Liliaceae, syn. Fritillaria roylei Hook) as acetylcholinesterase inhibitors.

Globally, Alzheimer's disease is an urgent public health concern with the ageing population in developing nations. Recent studies have identified isosteroidal alkaloids as promising therapeutic agents for Alzheimer's treatment. Fritillaria species are well-known rich sources of steroidal and isosteroidal alkaloids. In this context, the current study focuses on the biochemometric-guided isolation of three previously undescribed and two known isosteroidal alkaloids as acetylcholinesterase (AChE) inhibitors from the bulbs of Fritillaria cirrhosa D.Don. The isolated molecules were characterized by NMR, HR-ESI-MS, FT-IR, and DP4+ analysis. Subsequently, all isolates were evaluated for AChE inhibitory activity using Ellman's method. Among the evaluated molecules, 1 (IC50: 33.0 ± 4.4 μM) and 5 (IC50: 24.7 ± 4.5 μM) showed promising AChE inhibition in vitro. Enzyme kinetic studies of isolated molecules revealed mixed inhibition kinetics with Ki varying from 1.3 to 24.4 μM. Moreover, the in silico studies showed excellent binding affinities of isolated molecules with the target protein and good drug-like ADMET properties. The present study identified new isosteroidal alkaloids as promising AChE inhibitors from F. cirrhosa bulbs via a biochemometric approach and advocated their further exploration for treating neurodegenerative disorders.

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
Fitoterapia
Fitoterapia 医学-药学
CiteScore
5.80
自引率
2.90%
发文量
198
审稿时长
1.5 months
期刊介绍: Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.
×
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