Development of new drugs based on the metabolic activation by intestinal bacteria.

1.芍药苷衍生物的合成及其抗惊厥活性通过芍药苷与人肠道细菌Lactobacillus brevis在巯基化合物存在下的孵育反应，合成了17种不同的芍药苷衍生物，并对其抗惊厥活性进行了研究，其中8-（正己硫基）-、8-环戊硫基-、8-（对甲苯硫基）-和8-苯甲酰基硫基芍药苷具有较强的抗惊厥活性。最后一个化合物经柱层析分离后，7S-衍生物显示出最强的抗惊厥活性，而7 R-衍生物显示出肌肉松弛作用.大肠杆菌Rb_1的代谢产物（20 S）-原人参二醇20-O-葡萄糖苷（20 S-Protopanaxadiol 20-O-glucoside）对小鼠肿瘤转移有明显的抑制作用。其抗肿瘤转移作用机制研究表明，该代谢产物通过调节细胞周期蛋白D、p27 kip和c-myc等凋亡相关蛋白，诱导肿瘤细胞凋亡.肠道细菌介导的新反应的发展。将大黄酸转化为大黄蒽酮。去甲基化c.脱羟基在上述项目的研究过程中，我们分离出三种细菌菌株拟杆菌属，消化链霉菌属，和真杆菌属，从人类粪便中提取，它催化了新的反应a-c。

1. Synthesis of paeonimetabolin derivatives and their anti-convulsant activityBy incubation of paeoniflorin from peony roots with a human intestinal bacterium Lactobacillus brevis in the presence of mercapto compounds, 17 different kinds of paeonimetabolin derivatives were prepared and examined their anti-convulsant activity ; 8-(n-hexylthio)-, 8-cyclopentylthio-, 8-(p-tolylthio)-, and 8-benzoylthiopaeonimetabolin showed potent activity. After separation of the last compound by column chromatography, 7S-derivative showed the most potent anti-convulsant activity, but 7R-derivative showed the muscle relaxation effect.2. Effects of a metabolite of ginsenoside by intestinal bacteria on metastasis and apoptosis of tumor cellsA metabolite (20S)-protopanaxadiol 20-O-glucoside of ginsenoside Rb1 showed potent anti-metastatic action in mice. As to the mechanism of the anti-metastatic action, it was demonstrated that this metabolite induced apoptosis of the tumor cells by modulating apoptosis related proteins such as cyclin D, p27 kip and c-myc etc.3. Development of new reactions mediated by intestinal bacteria.a. Conversion of rhein to rhein anthroneb. Demethylationc. DehydroxylationDuring the investigation under the above project, we islated three bacterial strains Bacteroides sp., Peptostreptococcus sp., and Eubacterium sp., from human feces, which catalyzed the new reactions a-c.