Cytotoxic terpenoids from the stem bark of Taxus wallichiana

• Published in: Phytochemistry letters 2022-12, Vol.52, p.113-117
• Main Authors: Ngoc, Ninh Thi, Cuong, Dang Viet, Hanh, Tran Thi Hong, Cuong, Nguyen Xuan, Nam, Nguyen Hoai, Ha, Chu Hoang, Quang, Tran Hong
• Format: Article
• Language: English
• Subjects: Cyclopenta[b]naphthalene terpenoid; Cytotoxicity; Taxaceae; Taxane diterpenoid; Taxus wallichiana
• ISSN: 1874-3900; 1876-7486
• DOI: 10.1016/j.phytol.2022.10.004

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-deacetylbaccatin III (4), baccatin IV (5), 1-dehydroxybaccatin IV (6), 1-deoxybaccatin VI (7), taxol (8), 10-deacetyltaxol (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 μM. 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 μM), 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 μM. 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. [Display omitted] •15 compounds were isolated from Taxus wallichiana stem bark.•2 new and 13 known compounds were identified by spectroscopic analyses.•Cytotoxicity on SK-LU-1, HepG2, MCF7, SK-Mel-2, LNCaP, HEK-293A cell lines.