Terpenoids from Croton laevigatus Vahl and their antiviral activity.

Two rearranged ent-clerodanes, Crotonvigas A-B (1-2), eight other diterpenoids, Crotonvigas C-J (3-10), four previously undescribed sesquiterpenes, Crotonvigas KN (11-14), together with fourteen known terpenoids were isolated from Croton laevigatus Vahl. Among them, compound 1 is a chlorinated rearranged ent-clerodane. Its absolute configuration was unequivocally established by single-crystal X-ray diffraction. The anti-DENV activity results revealed compounds 5 and 24 inhibited DENV-prM protein expression stronger than ribavirin (RBV) exhibiting a potential anti-DENV activity, with the half-maximal effective concentration (EC50) values of 14.04 μM and 9.27 μM, the half-maximal cytotoxic concentration (CC50) values of 93.53 μM and 80.34 μM, and selectivity index (SI) values of 6.66 and 8.67, respectively. The anti-ZIKV activity revealed that compound 22 dose-dependently suppressed ZIKV E protein, with the EC50 value of 21.13 ± 1.58 μM, the CC50 value of >200 μM, and SI value of >9.47.