Three pairs of intriguing triterpenoid enantiomers from Lycopodium japonicum
摘要
Three pairs of intriguing triterpenoid enantiomers, named (-)-onocerin (1), (+)-onocerin (2), (-)-onocerin A (3), (+)-onocerin A (4), (-)-onocerin B (5), (+)-onocerin B (6), together with two biogenetically related triterpenoids, 3β,21α-dihydroxy-serrat-14-en-16-one (7) and serrat-14-ene-3β,21α-diol (8), were isolated from Lycopodium japonicum Thunb. New compound 1 and known compound 2 were one pair triterpenoid enantiomers, whose absolute configurations were determined by X-ray crystallographic analysis. Compounds 3/4 and 5/6 represent two pairs of new triterpenoid enantiomers, whose absolute configurations were determined by Mosher's ester method. This work provides an important new insight, being the first report on the identification of terpenoid enantiomers in Lycopodium species to our knowledge. Compounds 1–8 were evaluated for their acetylcholinesterase (AChE) inhibitory activities and the cytotoxic activit ies against four human cancer cell lines. Compounds 1, 3, and 5 demonstrated notable AChE inhibitory effects, showing IC50 values over 10-fold lower compared to their enantiomers, with values of 2.35 ± 0.22, 3.21 ± 0.12, and 3.62 ± 0.10 μM, respectively. Compounds 7 exhibited potent activities against four cancer cell lines (HeLa, MCF-7, A549, and MGC-803) with IC50 values of 1.86–36.74 μM. Molecular docking and molecular dynamics (MD) simulations of compounds 1–6 revealed that the observed differences in biological activity arise from conformational variations. These conformational differences result in distinct capacities of the enantiomers to access the active site pocket of AChE.