目的 采用具核梭杆菌和产肠毒素脆弱拟杆菌对化合物库(包括上市药物库和天然产物库)进行抑制剂筛选,以获得具有成药前景的抗肠道致病菌先导化合物.方法 本研究通过参考《厌氧菌药物敏感性试验方法-第七版》中的微量肉汤稀释法对5073个化合物进行体外抗肠道致病菌抑制活性筛选,并测定初筛阳性化合物对结肠癌细胞HCT116的抗肿瘤活性,以及致病菌与肿瘤细胞共孵育环境下化合物的抗肿瘤活性,从而获得具有抗肠道致病菌活性的先导化合物.结果 从5073个化合物中共获得240个具有抗肠道致病菌活性的化合物,初筛阳性率为4.73%;进一步测定它们对结肠癌细胞的体外抗肿瘤活性,获得48个具有明显抑制活性的化合物,总体阳性率为0.95%.结论 基于生物活性化合物库的表型筛选可以有效识别活性化合物,发现有潜力的苗头化合物和先导化合物,为发现新型小分子抗感染和抗肿瘤药物提供有效工具.
Objective To screen inhibitors in the compound library(including the marketed drug library and the natural product library)with Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis to obtain the leading compound against intestinal pathogens with the prospect of being a patent drug.Methods Totally 5073 compounds were screened for their in vitro anti-intestinal pathogenic bacteria inhibitory activities by referring to the microbroth dilution method in the"Anaerobic bacteria drug Sensitivity Test Method(7th Edition)".The antitumor activities of the positive compound against colon cancer cell HCT116,as well as the co-incubation environment of pathogenic bacteria and tumor cells were determined to obtain the leading compounds with anti-intestinal pathogenic bacteria activity.Results Totally 240 active compounds were obtained,and the positive rate was 4.73%.The antitumor activity of these compounds against the colon cancer cells in vitro was further determined,and 48 compounds with obvious inhibitory activity were obtained,with an overall positive rate of 0.95%.Conclusion Phenotypic screening based on bioactive compound library can effectively identify active compounds,find potential seedling compounds and leading compounds,and provide an effective tool for the discovery of novel small molecule anti-infection and anti-tumor drugs.