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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Screening for potent and selective anticlostridial leads among FDA-approved drugs
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Screening for potent and selective anticlostridial leads among FDA-approved drugs

机译：用于FDA批准的药物中有效和选择性的抗限型铅的筛选

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Clostridium difficile is a leading cause of morbidity and mortality particularly in hospital settings. In addition, treatment is very challenging due to the scarcity of effective therapeutic options. Thus, there remains an unmet need to identify new therapeutic agents capable of treating C. difficile infections. In the current study, we screened two FDA-approved drug libraries against C. difficile. Out of almost 3200 drugs screened, 50 drugs were capable of inhibiting the growth of C. difficile. Remarkably, some of the potent inhibitors have never been reported before and showed activity in a clinically achievable range. Structure-activity relationship analysis of the active hits clustered the potent inhibitors into four chemical groups; nitroimidazoles (MIC50 = 0.06-2.7 mu M), salicylanilides (MIC50 = 0.2-0.6 mu M), imidazole antifungals (MIC50 = 4.8-11.6 mu M), and miscellaneous group (MIC50 = 0.4-22.2 mu M). The most potent drugs from the initial screening were further evaluated against additional clinically relevant strains of C. difficile. Moreover, we tested the activity of potent inhibitors against representative strains of human normal gut microbiota to investigate the selectivity of the inhibitors towards C. difficile. Overall, this study provides a platform that could be used for further development of potent and selective anticlostridial antibiotics.
机译：Clostridium艰难术是一种尤其是医院环境中发病率和死亡率的主要原因。此外，由于有效治疗选择的稀缺性，治疗非常具有挑战性。因此，仍然需要识别能够治疗艰难梭菌感染的新治疗剂。在目前的研究中，我们筛选了两种核心核心的FDA批准的药物文库。在筛选的近3200种药物中，50种药物能够抑制C.艰难梭菌的生长。值得注意的是，在临床可实现的范围之前从未报告过一些强效抑制剂。活性击中的结构 - 活性关系分析将有效的抑制剂聚集成四种化学基团; Nitroimidazoles（MIC50 = 0.06-2.7 mu m），水杨酸盐（MIC50 =0.2-0.6μm），咪唑抗真菌（MIC50 =4.8-11.6μm）和杂项组（MIC50 =0.4-22.2μm）。来自初始筛查中最有效的药物进一步评估另外的临床相关的C.艰难素菌株。此外，我们测试了有效抑制剂免受人普通肠道微生物的代表性菌株的活性，以研究抑制剂对C.艰难梭菌的选择性。总体而言，本研究提供了一种平台，可用于进一步发展有效和选择性的抗细胞抗生素。

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