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 , 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","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 , 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\",\"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}
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.
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.