The polar neutral and basic taxoids isolated from needles and twigs of Taxus cuspidata and their biological activity |
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Authors: | Liyan Wang Liming Bai Daisuke Tokunaga Yusuke Watanabe Toshiaki Hasegawa Jun-ichi Sakai Wanxia Tang Yuhua Bai Katsutoshi Hirose Takao Yamori Akihiro Tomida Takashi Tsuruo Masayoshi Ando |
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Institution: | 2. Graduate School of Science and Technology, Niigata University, Niigata, 950-2181, Japan 3. Department of Chemistry and Chemical Engineering, Niigata University, Niigata, 950-2181, Japan 4. KNC Laboratories Co. Ltd., Kobe, Hyogo, 651-2271, Japan 5. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan 6. 22-20 Keiwa-machi, Taihaku-ku, Sendai, 982-0823, Japan
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Abstract: | Twelve basic taxoids and 22 neutral taxoids were isolated from basic and polar neutral fractions of the extracts of needles
and twigs of Taxus cuspidata. Among them, taxine NA-13, 3,11-cyclotaxinine NN-1, taxinine NN-6, 11(15→1)abeo-taxinine NN-1, taxine NA-8, and taxine NA-4 were isolated first from natural sources by us. The cytotoxic activity of isolated
compounds was evaluated against three human cell lines: normal human fibroblast cells (WI-38), malignant tumor cells induced
from WI-38 (VA-13), and human liver tumor cells (HepG2). 7-Epitaxol, 7-epicephalomannine, taxinine NN-6, taxine NA-2, taxuspine
H, and taxagifine were active toward VA-13 cells and 7-epitaxol, 7-epicephalomannine, taxinine NN-1, 9,10-deacetyltaxinine,
and taxagifine were active toward HepG2 cells. The multidrug-resistant (MDR) cancer reversal activity of isolated compounds
was evaluated on the basis of the amount of vincristine (VCR) accumulated in MDR human ovarian cancer 2780 AD. Taxine NA-8,
taxine NA-2, 5-cinnamoyl-10-acetyltaxicin II, and taxinine NN-1 indicated stronger MDR cancer reversal activity than verapamil.
The result of primary screening based on 39 human cancer cell lines suggests that taxinine NN-1 belongs to a new mechanistic
class and is a new anticancer agents. 7-Epicephalomannine was found to be an effective anticancer agent with tubulin as its
molecular target, which is the same as paclitaxel.
Part of this work was presented at the 74th Annual Meeting of the Chemical Society of Japan, Tanabe, March 1998, and the 41st
Symposium on the Chemistry of Terpenes, Essential Oils, and Aromatics, Gifu, December 1998. The results of this work were
also presented as patent documents at PCT Int: Appl WO 2001007040 A1, February 2001; Appl WO 2000-Jp 5036, 27 July 2000. Priority:
JP 1999-214273, 28 July 1999; JP 1999-224652, 6 August 1999; JP 2000-76404, 14 March 2000 |
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Keywords: | Taxus cuspidata Taxoid Cytotoxic activity MDR-cancer reversal activity Taxinine NN-1 |
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