Cytotoxic terpenoids from the stem bark of Taxus wallichiana

Chemical study of the stem bark of Taxus wallichiana Zucc. afforded the isolation of two new cyclopenta[b] naphthalene terpenoids, wallichianones A (1) and B (2) and 13 taxane diterpenoids, baccatin III (3), 10-deace-tylbaccatin III (4), baccatin IV (5), 1-dehydroxybaccatin IV (6), 1-deoxybaccatin VI (7), taxol (8), 10-deacetyl-taxol (9), 7-epi-10-deacetyltaxol (10), taxol-7-xyloside (11), 7-xylosyl-10-deacetyltaxol C (12), cephalomannine (13), 10-deacetylcaphalomannine (14), and 7-epi-10-deacetylcephalomannine (15). Their structures were identified by comprehensive analyses of the spectroscopic methods, including NMR and mass spectra. The absolute configurations of 1 and 2 were clarified by time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectroscopic analyses. Compounds 3 and 7-15 showed cytotoxicity against all five human cancer cell lines, including lung (SK-LU-1), liver (HepG2), breast (MCF7), skin (SK-Mel-2), and prostate (LNCaP), with IC50 values ranging from 1.4 +/- 0.2 to 88.1 +/- 5.8 mu M. Compounds 9-11, 14, and 15 were additionally cytotoxic against human embryonic kidney (HEK-293A) cell line (IC50 = 14.5 +/- 1.0-48.4 +/- 1.0 mu M), however, 13 was noncytotoxic toward this cell line. The positive control, ellipticine showed cytotoxicity against all the cell lines, with IC50 values in a range of 1.5 +/- 0.1-2.0 +/- 0.3 mu M. Preliminary analysis of the structural and cytotoxicity relationship of compounds 3-15 suggested that the phenylalanine substituent at C-13 may contribute an important role for the cytotoxicity of the taxane diterpenoids.