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":"<div><div>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. <em>Fritillaria</em> 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 <em>Fritillaria cirrhosa</em> 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, <strong>1</strong> (IC<sub>50</sub>: 33.0 ± 4.4 μM) and <strong>5</strong> (IC<sub>50</sub>: 24.7 ± 4.5 μM) showed promising AChE inhibition <em>in vitro</em>. Enzyme kinetic studies of isolated molecules revealed mixed inhibition kinetics with <em>K</em><sub><em>i</em></sub> varying from 1.3 to 24.4 μM. Moreover, the <em>in silico</em> 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 <em>F. cirrhosa</em> bulbs <em>via</em> a biochemometric approach and advocated their further exploration for treating neurodegenerative disorders.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"180 ","pages":"Article 106279"},"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\":\"<div><div>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. <em>Fritillaria</em> 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 <em>Fritillaria cirrhosa</em> 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, <strong>1</strong> (IC<sub>50</sub>: 33.0 ± 4.4 μM) and <strong>5</strong> (IC<sub>50</sub>: 24.7 ± 4.5 μM) showed promising AChE inhibition <em>in vitro</em>. Enzyme kinetic studies of isolated molecules revealed mixed inhibition kinetics with <em>K</em><sub><em>i</em></sub> varying from 1.3 to 24.4 μM. Moreover, the <em>in silico</em> 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 <em>F. cirrhosa</em> bulbs <em>via</em> a biochemometric approach and advocated their further exploration for treating neurodegenerative disorders.</div></div>\",\"PeriodicalId\":12147,\"journal\":{\"name\":\"Fitoterapia\",\"volume\":\"180 \",\"pages\":\"Article 106279\"},\"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://www.sciencedirect.com/science/article/pii/S0367326X24004623\",\"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://www.sciencedirect.com/science/article/pii/S0367326X24004623","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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.
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.