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

Abstract

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.