Shu-Shuai Chen , Cheng-Yu Zheng , Guan-Zhou Yang , Jun-Su Zhou , Shi-Jun He , Yao-Yue Fan , Jian-Min Yue
{"title":"Highly oxygenated steroids with immunosuppressive activity from Solanum undatum†","authors":"Shu-Shuai Chen , Cheng-Yu Zheng , Guan-Zhou Yang , Jun-Su Zhou , Shi-Jun He , Yao-Yue Fan , Jian-Min Yue","doi":"10.1039/d4ob01642d","DOIUrl":null,"url":null,"abstract":"<div><div> <em>Solanum undatum</em> is a medicinal plant used for the treatment of oedema, rheumatoid arthritis and toothache, from which seven highly oxygenated steroids (), including three new ones (), have been characterized. Compound is a new steroidal carboxylic acid featuring a cyclohexa-2,5-dien-1-one moiety and compounds and are new withanolide analogs with a 1,6-dimethyl-3,7-dioxabicyclo[4.1.0]heptan-2-ol terminus. Their structures and absolute configurations were determined by a combination of spectroscopic data, quantum chemical calculations, single-crystal X-ray diffraction, and the NMR-based phenylglycine methyl ester (PGME) method. An immunosuppressive activity assay revealed that compounds exhibited substantial activities against the proliferation of T and B lymphocytes <em>in vitro</em>, with IC<sub>50</sub> values ranging from 1.60 to 7.89 μM and 0.90 to 6.90 μM, respectively. Notably, compound showed selective inhibitory effect toward B cells with the highest selective index (SI = 40.5). Preliminary structure–activity relationships of compounds suggest that the terminal 1,6-dimethyl-3,7-dioxabicyclo[4.1.0]heptan-2-ol or 5,5-spiroacetal moiety is critical for immunosuppressive activity. Our study indicated that they could be promising lead compounds for immunosuppressive agents.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":"23 1","pages":"Pages 83-89"},"PeriodicalIF":2.9000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1477052024009704","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Solanum undatum is a medicinal plant used for the treatment of oedema, rheumatoid arthritis and toothache, from which seven highly oxygenated steroids (), including three new ones (), have been characterized. Compound is a new steroidal carboxylic acid featuring a cyclohexa-2,5-dien-1-one moiety and compounds and are new withanolide analogs with a 1,6-dimethyl-3,7-dioxabicyclo[4.1.0]heptan-2-ol terminus. Their structures and absolute configurations were determined by a combination of spectroscopic data, quantum chemical calculations, single-crystal X-ray diffraction, and the NMR-based phenylglycine methyl ester (PGME) method. An immunosuppressive activity assay revealed that compounds exhibited substantial activities against the proliferation of T and B lymphocytes in vitro, with IC50 values ranging from 1.60 to 7.89 μM and 0.90 to 6.90 μM, respectively. Notably, compound showed selective inhibitory effect toward B cells with the highest selective index (SI = 40.5). Preliminary structure–activity relationships of compounds suggest that the terminal 1,6-dimethyl-3,7-dioxabicyclo[4.1.0]heptan-2-ol or 5,5-spiroacetal moiety is critical for immunosuppressive activity. Our study indicated that they could be promising lead compounds for immunosuppressive agents.
期刊介绍:
Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.