neo-Clerodane Diterpenoids from Scutellaria barbata with Activity against Epstein-Barr Virus Lytic Replication

Bioassay-guided fractionation was conducted on an EtOAc-soluble extract of the whole plants of Scutellaria barbata, monitored by inhibition of Epstein-Barr virus (EBV) lytic replication. Twenty-six neo-clerodane diterpenoids were isolated, of which 13 are new (1-13, scutolides A-L) and 13 previously known (14-26). The structures of 1-13 were elucidated by analysis of their NMR and MS spectroscopic data. Furthermore, the configurations of the new compounds 1 and 11 were confirmed by single-crystal X-ray diffraction. All of the isolated compounds were evaluated for inhibitory effects against EBV lytic replication. Eleven compounds (3, 4, 6, 11, 12, 15, 16, 17, 20, 22, and 24) exhibited moderate to potent inhibition, with EC50 values from 3.2 to 23.6 mu M and selective index (SI) values from 2.1 to 109.2. More specifically, the new compound 4 showed the most potent activity, with EC50 and SI values of 3.2 mu M and 46.1, respectively, while compound 24 (EC50 = 16.4 mu M) exhibited the highest SI of 109.2. This study is the first to report that neo-clerodane diterpenoids demonstrate significant inhibition against EBV lytic replication.