微量热法比较黄连中四种生物碱的抗菌作用

采用微量热法研究和比较中药黄连中四种生物碱(BAs)的抗菌(大肠杆菌)作用。这四种生物碱分别为小檗碱、黄连碱、巴马汀和药根碱。用LKB-2277生物活性检测系统，以停留法测定了37 ℃时大肠杆菌在BAs作用下的热流功率-时间曲线，并记录生长速率常数k, 指数生长期和稳定期的最大热功率Pm, log、Pm, stat, 生长抑制率I, 传代时间tg，指数生长期的总产热量Qt, log，半数抑菌浓度IC50等热动力学参数。结果显示这四种生物碱具有相异的抗大肠杆菌生长代谢的作用，k, Pm, log和Qt, log值随BAs浓度的增加而相应的减少。综合分析k, Pm, log, Qt, log, I 和IC50值可以看出，BAs抑制大肠杆菌生长代谢强度按小檗碱、黄连碱、巴马汀、药根碱的顺序依次减弱。构效关系研究表明，母环C-2和C-3上连接的亚甲二氧基比甲氧基更能显著增强相应化合物的抗菌作用，而C-9和C-10上连接的亚甲二氧基或甲氧基对这种抗菌作用影响不大。

Comparison of Anti‐bacterial Activity of Four Kinds of Alkaloids in Rhizoma Coptidis Based on Microcalorimetry

The anti‐bacterial activities of four kinds of alkaloids in Rhizoma Coptidis, a traditional Chinese medicinal (TCM) herb, on Escherichia coli (E. coli) growth were investigated and compared by microcalorimetry. The four kinds of alkaloids were berberine, coptisine, palmatine and jatrorrhizine. The heat flow power‐time curves of E. coli growth in the presence of the four kinds of alkaloids were measured using an LKB‐2277 Bio‐activity monitor using a stop‐flow method, at 37°C. Then the thermal kinetic parameters such as, growth rate constant k, maximum power output of the log phase P_m,log and the stationary phase P_m,stat, growth inhibitory ratio I, generation time t_g, total heat output of the log phase Q_t,log and half‐inhibitory concentration of the drugs, IC₅₀, were obtained from the curves. The four kinds of alkaloids had different anti‐E. coli activities. k, P_m,log and Q_t,log of E. coli in the presence of the four kinds of alkaloids decreased with increasing concentrations of the alkaloids. Judged from the values of k, P_m,log, Q_t,log, I and IC₅₀, the experimental results revealed that the sequence of anti‐bacterial activities of the four kinds of alkaloids was berberine>coptisine>palmatine>jatrorrhizine. The functional groups methylenedioxy at C‐2 and C‐3 on phenyl ring improved anti‐bacterial activity more remarkably than methoxyl at C‐2 and C‐3 on the phenyl ring. However, the antibacterial activity did not vary significantly with methylenedioxy or methoxyl at C‐9 and C‐10 on the other phenyl ring.