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化学学报
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化学学报 ›› 2010, Vol. 68 ›› Issue (03): 205-210.    下一篇

研究论文

乌头类双酯型生物碱对嗜热四膜虫生长代谢的微量热学研究

唐慧英1,3，韩玉梅1,2，鄢丹*,1，张少锋1,3，罗云1,2，肖小河1，刘荣华3，彭成*,2   

  1. (1解放军中药研究所 解放军第三零二医院 北京 100039)
    (2成都中医药大学药学院 成都 610075)
    (3江西中医学院现代中药制剂教育部重点实验室 南昌 330004)
  • 投稿日期:2009-08-30 修回日期:2009-09-18 发布日期:2010-02-20
  • 通讯作者: 彭成 E-mail:yd277@126.com
  • 基金资助:

    国家“重大新药创制”科技重大专项课题（No.2009ZX09502-003）;国家自然科学基金项目（No.30873385）

Microcalorimetric Investigation of Toxic Effects of Diester Diterpenoid Alkaloids from Aconiti Class on Tetrahymena thermophila BF5 Growth

Tang Huiying1,3 Han Yumei1,2 Yan Dan*,1 Zhang Shaofeng1,3 Luo Yun1,2 Xiao Xiaohe1 Liu Ronghua3 Peng Cheng*,2   

  1. (1 Institute of Chinese Materia Medica, 302 Hospital of PLA, Beijing 100039)
    (2 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075)
    (3 Key Laboratory of Modern Preparation of TCM (Jiangxi University of Traditional Chinese Medicine), Ministry of Education, Nanchang 330004)
  • Received:2009-08-30 Revised:2009-09-18 Published:2010-02-20

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建立灵敏表征乌头类双酯型生物碱(DDA)对嗜热四膜虫生长代谢影响的评价方法. 采用微量热法, 在不同给药条件下, 以表达功率-时间曲线(热谱曲线)的特征参数生长速率常数(k)、半数抑制浓度(IC50)、最大输出功率(Pmax)及达峰时间(tp)和总产热量(Qt)为指标, 对嗜热四膜虫生长代谢程度进行客观地量化评价. 结果表明, 随着3种DDA浓度的增加, 达峰时间tp延长, 生长速率常数k、最大输出功率Pmax等随之降低, 且生长速率常数k与相应的浓度间呈现良好的线性关系: r乌头碱＝0.9910 (IC50＝207.7 μg•mL－1); r新乌头碱＝0.9923 (IC50＝412.5 μg•mL－1); r次乌头碱＝0.9977 (IC50＝1497 μg•mL－1). 同时由半抑制浓度IC50得到3种DDA毒性的大小顺序: 乌头碱＞新乌头碱＞次乌头碱. 初步构效关系研究表明, 在化合物C(3)上引入羟基(OH)以及N原子上引入乙基(CH2CH3)均可明显增加双酯型生物碱对嗜热四膜虫的毒性作用.

关键词: 微量热法, 双酯型生物碱, 嗜热四膜虫, 生长代谢

The effect of diester diterpenoid alkaloids (DDA) from aconiti class on the growth of Tetrahymena thermophila BF5 was investigated by means of the TAM III isothermal microcalorimetric system. The extent and duration of toxic effects on the metabolism were evaluated by studying the growth rate constant (k), half inhibitory ratio (IC50), maximum heat-output power (Pmax), peak time of maximum heat-output power (tp) and total heat production (Qt). Experimental results showed that the value of tp increased with increasing the concentration of DDA. Moreover, the value of k and Pmax were reduced with increasing the concentrations of the three drugs. Furthermore, the growth rate constant (k) was linked to the concentration of DDA: raconitine＝0.9910 (IC50＝207.7 μg•mL－1); rmesaconitine＝0.9923 (IC50＝412.5 μg•mL－1); rhypaconitine＝0.9977 (IC50＝1497 μg•mL－1). The sequence of toxic effects of the three DDA is aconitine＞mesaconitine＞hypaconitine. It was suggested that the hydroxy group at C(3) and ethyl group connectted with nitrogen could possibly improve the toxic effects of DDA on Tetrahymena thermophila BF5 growth.

Key words: microcalorimetry, diester diterpenoid alkaloid, Tetrahymena thermophila BF5, growth, metabolism