Highly oxygenated steroids with immunosuppressive activity from Solanum undatum†

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.