Cytotoxic C-20 non-oxygenated ent-kaurane diterpenoids from Isodon wardii

Twenty new ent-kaurane diterpenoids, wardiisins A-T (1-20), along with two previously undescribed artefactual compounds (21 and 22) and twelve known analogues (23-34), were isolated from the aerial part of Isodon wardii. Their structures were elucidated by comprehensive analysis of spectroscopic data and single-crystal X-ray diffraction, and most of them were found to bear unusual C-12 oxygenation. Compounds 4, 7, 8, 19, 20, 21 exhibited remarkable cytotoxicity against the cancer cell lines HL-60, SMMC-7721, A-549, MDA-MB-231, and SW480, with IC₅₀ values ranging from 0.3 to 5.2 μM. Moreover, 7 was found to induce G2/M cell cycle arrest and promote apoptosis in SW480 cell lines.