Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus

Two pairs of novel pentacyclic spermidine alkaloids enantiomers, (±)-Orychoviolines A and B ((±)-1 and (±)-2), were isolated from the seeds of Orychophragmus violaceus and represented the first example of 2-Piperidinone-fused Hydrodibenzofuran skeleton, constructed from a 6/5/6/6 tetracyclic system and an 18 atomic ring. Most unexpected novelty was formation of one more piperidinone ring by a connection between C-6 and N-7. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray crystallography, and ECD. Compared to Ex-RAD (sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone), (-)-1 exhibited a significant radioprotective effect on cell survival and DNA damage. (-)-1 also exhibited remarkable anti-inflammatory activity by inhibiting the production of NO in RAW 264.7 cells activated by lipopolysaccharide with IC50 value of 20.3 ± 1.58 μM, which was equivalent to that of Dexamethasone.