手性吡咯烷作为阿尔茨海默病和神经退行性疾病的多效制剂。

IF 3.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Antonio Carrieri , Alexia Barbarossa , Modesto de Candia , Francesco Samarelli , Cosimo Damiano Altomare , Kinga Czarnota-Łydka , Sylwia Sudoł-Tałaj , Gniewomir Latacz , Jadwiga Handzlik , Leonardo Brunetti , Luca Piemontese , Francesco Limongelli , Giovanni Lentini , Alessia Carocci
{"title":"手性吡咯烷作为阿尔茨海默病和神经退行性疾病的多效制剂。","authors":"Antonio Carrieri ,&nbsp;Alexia Barbarossa ,&nbsp;Modesto de Candia ,&nbsp;Francesco Samarelli ,&nbsp;Cosimo Damiano Altomare ,&nbsp;Kinga Czarnota-Łydka ,&nbsp;Sylwia Sudoł-Tałaj ,&nbsp;Gniewomir Latacz ,&nbsp;Jadwiga Handzlik ,&nbsp;Leonardo Brunetti ,&nbsp;Luca Piemontese ,&nbsp;Francesco Limongelli ,&nbsp;Giovanni Lentini ,&nbsp;Alessia Carocci","doi":"10.1016/j.bmc.2024.117829","DOIUrl":null,"url":null,"abstract":"<div><p>In pharmaceutical science and drug design the versatility of the pyrrolidine scaffold relating to spatial arrangement, synthetic accessibility and pharmacological profile is a largely explored and most likely interesting one. Nonetheless, few evidences suggest the pivotal role of pyrrolidine as scaffold for multipotent agents in neurodegenerative diseases. We then challenged the enrolling in the field of Alzheimer disease of so far not ravelled targets of this chemical cliché with a structure based and computer-aided design strategy focusing on multi-target action, versatile synthesis as well as pharmacological safeness. To achieve these hits, ten enantiomeric pairs of compounds were obtained and tested, and the biological data will be here presented and discussed. Among the novel compounds, coumarin and sesamol scaffolds containing analogues resulted promising perspectives.</p></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968089624002438/pdfft?md5=f1a68b9d04ceec35053cf671326cabbf&pid=1-s2.0-S0968089624002438-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Chiral pyrrolidines as multipotent agents in Alzheimer and neurodegenerative diseases\",\"authors\":\"Antonio Carrieri ,&nbsp;Alexia Barbarossa ,&nbsp;Modesto de Candia ,&nbsp;Francesco Samarelli ,&nbsp;Cosimo Damiano Altomare ,&nbsp;Kinga Czarnota-Łydka ,&nbsp;Sylwia Sudoł-Tałaj ,&nbsp;Gniewomir Latacz ,&nbsp;Jadwiga Handzlik ,&nbsp;Leonardo Brunetti ,&nbsp;Luca Piemontese ,&nbsp;Francesco Limongelli ,&nbsp;Giovanni Lentini ,&nbsp;Alessia Carocci\",\"doi\":\"10.1016/j.bmc.2024.117829\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In pharmaceutical science and drug design the versatility of the pyrrolidine scaffold relating to spatial arrangement, synthetic accessibility and pharmacological profile is a largely explored and most likely interesting one. Nonetheless, few evidences suggest the pivotal role of pyrrolidine as scaffold for multipotent agents in neurodegenerative diseases. We then challenged the enrolling in the field of Alzheimer disease of so far not ravelled targets of this chemical cliché with a structure based and computer-aided design strategy focusing on multi-target action, versatile synthesis as well as pharmacological safeness. To achieve these hits, ten enantiomeric pairs of compounds were obtained and tested, and the biological data will be here presented and discussed. Among the novel compounds, coumarin and sesamol scaffolds containing analogues resulted promising perspectives.</p></div>\",\"PeriodicalId\":255,\"journal\":{\"name\":\"Bioorganic & Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0968089624002438/pdfft?md5=f1a68b9d04ceec35053cf671326cabbf&pid=1-s2.0-S0968089624002438-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic & Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0968089624002438\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968089624002438","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

在制药科学和药物设计领域,吡咯烷支架在空间布局、合成可及性和药理特征方面的多功能性是人们探索的重点,也是最有可能引起人们兴趣的一个方面。然而,很少有证据表明吡咯烷作为神经退行性疾病多能药物的支架具有关键作用。因此,我们采用基于结构和计算机辅助的设计策略,重点关注多靶点作用、多功能合成以及药理学安全性,对阿尔茨海默病领域迄今尚未发现的这种化学陈词滥调的靶点提出了挑战。为了实现这些目标,我们获得并测试了十对化合物的对映体,并将在此介绍和讨论其生物数据。在这些新化合物中,含有香豆素和芝麻酚支架的类似物具有广阔的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Chiral pyrrolidines as multipotent agents in Alzheimer and neurodegenerative diseases

Chiral pyrrolidines as multipotent agents in Alzheimer and neurodegenerative diseases

In pharmaceutical science and drug design the versatility of the pyrrolidine scaffold relating to spatial arrangement, synthetic accessibility and pharmacological profile is a largely explored and most likely interesting one. Nonetheless, few evidences suggest the pivotal role of pyrrolidine as scaffold for multipotent agents in neurodegenerative diseases. We then challenged the enrolling in the field of Alzheimer disease of so far not ravelled targets of this chemical cliché with a structure based and computer-aided design strategy focusing on multi-target action, versatile synthesis as well as pharmacological safeness. To achieve these hits, ten enantiomeric pairs of compounds were obtained and tested, and the biological data will be here presented and discussed. Among the novel compounds, coumarin and sesamol scaffolds containing analogues resulted promising perspectives.

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
Bioorganic & Medicinal Chemistry
Bioorganic & Medicinal Chemistry 医学-生化与分子生物学
CiteScore
6.80
自引率
2.90%
发文量
413
审稿时长
17 days
期刊介绍: Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
×
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