Diversified abietane family diterpenoids from the leaves of Leucosceptrurn canum and their cytotoxic activity

Twenty-four diterpenoids of abietane family, including thirteen undescribed compounds and eleven known ones, were isolated from the leaves of Leucosceptrurn canum. Their structures were elucidated by comprehensive spectroscopic analyses (including 1D and 2D-NMR and HRMS), and in the case of 15-hydroxy-abieta-8,11,13-trien-3-one by single-crystal X-ray diffraction. Their frameworks are highly diversified, involving normal abietane, 9,10-epoxy-9,10-seco-abietane, 18(4 -> 3)-abeo-abietane, 3,4-seco-18(4 -> 3)-abeo-abietane, and 16-norabietane. Selected compounds were evaluated for their cytotoxic activity against three human tumor cell lines, NCI-H1975, HepG2 and MCF-7. Among them, 3 beta-hydroxy-abieta-8,13-diene, 3 beta-hydroxy-abieta-8,11,13,15-tetraene, and 3 beta-hydroxy-9,10-epoxy-9,10-seco-abieta-8,11,13-triene exhibited moderate cytotoxicity against all three cell lines with IC50 values ranging from 8.11 to 50.73 mu M, while 3 alpha-hydroxy-abieta-8,11,13,15-tetraene, 3 beta-hydroxy-abieta-8,11,13,15-tetraen-7-one, and 15-hydroxy-18(4 -> 3)-abeo-abieta-3,8,11,13-tetraene were selectively active with IC50 values ranging from 28.80 to 71.29 mu M.