Dolabellane and Clerodane Diterpenoids from the Twigs and Leaves of Casearia kurzii

A pair of enantiomeric 15-nordolabellane diterpenoids, (−)- and (+)-caseadolabellols A ( 1a and 1b ), three dolabellane diterpenoids, caseadolabellols B–D ( 2 – 4 ), two dolastane diterpenoids, caseadolastols A and B ( 5 and 6 ), 10 clerodane diterpenoids, caseakurzins A–J ( 7 – 16 ), and nine known diterpenoids ( 17 – 25 ) were isolated from the twigs and leaves of Casearia kurzii . The structures of the new compounds were established on the basis of extensive spectroscopic data, and those of compounds 1a, 1b, and 2 were verified by single-crystal X-ray crystallographic analysis. The enantiomers 1a and 1b were separated by chiral-phase HPLC. The absolute configurations were determined by experimental and calculated ECD data, the modified Mosher’s method, or literature comparison. Compounds 1a and 5 showed significant quinone reductase-inducing activity in Hepa 1c1c7 cells, while 1b showed moderate activity. Molecular docking studies showed that 1a had greater binding affinity with Nrf2 protein (5FNQ) than 1b . The cytotoxic activity of compounds 1a, 1b, 2 – 12, 15, and 16 was evaluated, among which compounds 8 and 16 exhibited significant inhibitory activity against the A549 cell line. Compounds 8 and 16 induced the A549 cells to arrest at G2/M and S phases, respectively, and both compounds induced apoptosis in A549 cells.