ent-Rosane diterpenoids from Euphorbia milii showing an Epstein–Barr virus lytic replication assay

The phytochemical investigation on the acetone extract of Euphorbia milii afforded thirteen new ent -rosane diterpenoids ( 1–13 ) through bioassay guided fractionation for evaluating its effect on Epstein–Barr virus (EBV) DNA lytic replication. Structures were determined by comprehensive spectroscopic analyses including 1D & 2D NMR techniques, chemical methods, and experimental and calculated electronic circular dichroism (ECD) data. The absolute configuration of euphominoid A ( 1 ) was established by single crystal X-ray diffraction analysis of its p -bromobenzoate derivative 1a . Compounds 1–3 , and 10 displayed inhibitory activity with EC 50 values ranging from 5.4 to 29.1 μM and selective index (SI) values varied from 4.5 to 9.3. Compound 2 showed the most potent inhibitory activity with an EC 50 value of 5.4 μM comparing with the positive control (+)-rutamarin (EC 50 = 5.4 μM). This is the first report of ent -rosane-type diterpenoids exhibiting significant inhibition of EBV lytic replication.