Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 4-1, Maeda 7-jo 15-choume, Teine-ku, Sapporo, 006-8585, Japan.
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599 7568, USA.
J Nat Med. 2020 Jan;74(1):83-89. doi: 10.1007/s11418-019-01346-z. Epub 2019 Jul 25.
We explored new cytotoxic C-diterpenoid alkaloid, lipojesaconitine (1), from rhizoma of Aconitum japonicum THUNB. subsp. subcuneatum (NAKAI) KADOTA. Two additional non-cytotoxic new C-diterpenoid alkaloids, 10-hydroxychasmanine (2) and 3-hydroxykaracoline (3), together with eight known C- and C-diterpenoid alkaloids (4-11) were also isolated. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Six known diterpenoid alkaloids, foresticine (5), neolinine (6), aconicarchamine A (7), 9-hydroxynominine (8), kobusine (9), and torokonine (10), were isolated for the first time from A. japonicum subsp. subcuneatum. Alkaloid 1 showed cytotoxicity with IC values ranging from 6.0 to 7.3 µM against four human tumor cell lines, except a multidrug-resistant subline, suggesting that 1 was likely exported by P-glycoprotein.
我们从乌头属植物（Aconitum japonicum THUNB. subsp. subcuneatum (NAKAI) KADOTA）的根茎中探索到了一种新型细胞毒性 C-二萜生物碱，脂乌头碱（1）。此外，还分离得到了另外两种非细胞毒性的新型 C-二萜生物碱，10-羟基船形乌头碱（2）和 3-羟基卡拉可林碱（3），以及八种已知的 C-和 C-二萜生物碱（4-11）。通过广泛的光谱方法，包括 NMR（1D 和 2D）、IR 和 MS（HRMS），确定了它们的结构。六种已知的二萜生物碱，森林碱（5）、新乌宁碱（6）、 aconicarchamine A（7）、9-羟基 nominine（8）、kobusine（9）和 torokonine（10），首次从乌头属植物亚种 subcuneatum 中分离得到。生物碱 1 对四种人类肿瘤细胞系表现出细胞毒性，IC 值范围为 6.0 至 7.3 μM，除了一种多药耐药亚系外，这表明 1 可能被 P-糖蛋白外排。
