Bioactive constituents of Thuja occidentalis

An ethyl acetate-soluble extract of the combined leaves and twigs of Thuja occidentalis was found to inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA )-induced ornithine decarboxylase (ODC) in cultured mouse epidermal ME 308 cells. Bioassay-guided fractionation of this extract led to the isolation o f six active constituents (1-6), namely, (+)-7-oxo-13-epi-pimara-14,15-dien -18-oic acid (1), (+)-7-oxo-13-epipimara-8,15-dien- 18-oic acid (2), (+)-is opimaric acid (3), (1S,2S,3R)-(+)-isopicrodeoxypodophyllotoxin (4), (-)-deo xypodophyllotoxin (5), and (-)-deoxypodorhizone (6). Compounds 1 and 4 are new natural products, and their structures and stereochemistry were determi ned using spectroscopic methods. Compounds 1-6 were evaluated for inhibitio n of the transformation of murine epidermal JB6 cells, inhibition of ornith ine decarboxylase induction with murine epidermal ME 308 cells, and cytotox ic activity against KB cells.