目的 从传统中药蟾酥中寻找抗肿瘤活性强而毒性低的化合物。方法 采用追踪分离的方式,以体外肿瘤细胞生长抑制强度为活性指标,同时结合小鼠急性毒性实验,对蟾酥的主要化学成分进行初步研究。结果 采用活性追踪分离方式,从蟾酥中分离得到具有抑制肿瘤细胞生长活性同时对小鼠急性毒性较低的化合物蟾毒它灵,其对人非小细胞肺癌A549细胞具有较好的生长抑制作用,小鼠iv给药的LD50约为蟾毒灵的4倍,而且稳定性较好。结论 综合化合物的活性、毒性及稳定性等因素,初步判断蟾毒它灵较其他同类化合物具有更好的抗肿瘤药物开发前景。

Objective To obtain antitumor active compounds with lower toxicity from main ingredients of Chinese materia medica Bufonis Venenum. Methods Taking inhibition of in vitro tumor cells as active indexes, a bioassay-guided separation and toxicity evaluation in mice of ingredients in Bufonis Venenum were applied. Results Bufotalin was seperated from Bufonis Venenum with significant inhibition and lower acute toxicity by active tracking method. The inhibitory effect on the proliferation of A549 was better, LD50 of bufotalin by iv administration to mice is about four times of bufalin, and bufotalin is stable. Conclusion Integrated the activity, toxicity, and stability factors of the compounds, bufotalin from Bufonis Venenum will deserve further research than any other similar compounds in potential antitumor activity.

国家重大科技专项(2009ZX09103-385)