Highly oxygenated steroids with immunosuppressive activity from

• Published in: Organic & biomolecular chemistry 2024-12, Vol.23 (1), p.83-89
• Main Authors: Chen, Shu-Shuai, Zheng, Cheng-Yu, Yang, Guan-Zhou, Zhou, Jun-Su, He, Shi-Jun, Fan, Yao-Yue, Yue, Jian-Min
• Format: Article
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d4ob01642d

Solanum undatum is a medicinal plant used for the treatment of oedema, rheumatoid arthritis and toothache, from which seven highly oxygenated steroids ( 1-7 ), including three new ones ( 1-3 ), have been characterized. Compound 1 is a new steroidal carboxylic acid featuring a cyclohexa-2,5-dien-1-one moiety and compounds 2 and 3 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 2-7 exhibited substantial activities against the proliferation of T and B lymphocytes in vitro , with IC 50 values ranging from 1.60 to 7.89 μM and 0.90 to 6.90 μM, respectively. Notably, compound 6 showed selective inhibitory effect toward B cells with the highest selective index (SI = 40.5). Preliminary structure-activity relationships of compounds 1-7 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. Solanum undatum is a medicinal plant used for the treatment of oedema, rheumatoid arthritis and toothache, from which seven highly oxygenated steroids ( 1-7 ), including three new ones ( 1-3 ), have been characterized.