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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=207.7μg·mL-1);r新乌头碱=0.9923(IC50=412.5μg·mL-1);r次乌头碱=0.9977(IC50=1497μg·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.
A sensitive method for characterizing the effect of Aconitum diolate alkaloids (DDA) on the growth and metabolism of Tetrahymena thermophila was established.Using calorimetry, under different administration conditions, the expression of power-time curve (thermogram) (K), IC50, Pmax, tp and Qt of the characteristic parameters of the thermophilic Tetrahymena thermophila Objectively and quantitatively.The results showed that with the increase of three DDA concentrations, the peak time tp was prolonged, the growth rate constant k and the maximum output power Pmax decreased, and the growth rate constant k and the corresponding concentration showed good Linear correlation: r Aconitine = 0.9910 (IC50 = 207.7 μg · mL -1); r Mesaconitine = 0.9923 (IC50 = 412.5 μg · mL -1); r Aconitine = 0.9977 (IC50 = 1497 μg · mL-1) .According to the half-inhibitory concentration (IC50), the order of the three toxicities of DDA was aconitine> mesaconitine> hypaconitine.The preliminary structure-activity relationship study showed that hydroxyl group (OH) and the introduction of ethyl (CH2CH3) on the N atom can significantly increase the toxic effect of the diester alkaloids on Tetrahymena thermophila.