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

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(P_max)及达峰时间(t_p)和总产热量(Q_t)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t_p延长, 生长速率常数k、最大输出功率P_max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.

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

The effect of diester diterpenoid alkaloids (DDA) from aconiti class on the growth of Tetrahy-mena 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 (κ), half inhibitory ratio (IC_(50)), maximum heat-output power (P_(max)), peak time of maximum heat-output power (t_p) and total heat production (Q_t). Experimental results showed that the value of tp increased with in-creasing the concentration of DDA. Moreover, the value of k and P_(max) were reduced with increasing the concentrations of the three drugs. Furthermore, the growth rate constant (κ) was linked to the concentration of DDA: r_(aconitine)=0.9910 (IC_(50)=207.7 μg·mL~(-1)); r_(mesaconitine)=0.9923 (IC_(50)=412.5 μg·mL~(-1)); r_(hypaconitine)=0.9977 (IC_(50)= 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. Keywords microcalorimetry; diester diterpenoid alkaloid; Tetrahymena thermophila BF5; growth; me-tabolism