Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
J Med Chem. 2023 Oct 26;66(20):13891-13899. doi: 10.1021/acs.jmedchem.3c01249. Epub 2023 Sep 21.
is an anaerobic Gram-positive bacterium that colonizes the gut of patients treated with broad-spectrum antibiotics. The normal gut microflora prevents . colonization; however, dysbiosis by treatment with broad-spectrum antibiotics causes recurrent . infection (CDI) in 25% of patients. There are no fully effective antibiotics for multiple recurrent CDIs. We report herein that oxadiazole antibiotics exhibit bactericidal activity against . vegetative cells. We screened a library of 75 oxadiazoles against . ATCC 43255. The findings from this collection served as the basis for the syntheses of an additional 58 analogs, which were tested against the same strain. We report a potent (MIC = 0.5 μg/mL and MIC = 1 μg/mL values for 101 . strains) and narrow-spectrum oxadiazole (3-(4-(cyclopentyloxy)phenyl)-5-(4-nitro-1-imidazol-2-yl)-1,2,4-oxadiazole; compound ), which is not active against common gut bacteria or other tested organisms. Compound is selectively bactericidal against . and targets cell-wall synthesis.
艰难梭菌是一种厌氧的革兰氏阳性细菌，定植于接受广谱抗生素治疗的患者的肠道中。正常的肠道微生物群可防止艰难梭菌定植；然而，广谱抗生素治疗引起的微生态失调可导致 25%的患者反复发生艰难梭菌感染（CDI）。对于多次反复发生的 CDI，目前尚无完全有效的抗生素。我们在此报告，恶二唑类抗生素对艰难梭菌的营养细胞具有杀菌活性。我们针对艰难梭菌 ATCC 43255 对 75 种恶二唑类化合物进行了筛选。该文库的研究结果为合成另外 58 种类似物提供了依据，并用相同的菌株对这些类似物进行了测试。我们报告了一种强效的（MIC 值为 0.5 μg/mL 和 1 μg/mL，对 101 株艰难梭菌的 MIC 值）和窄谱恶二唑类化合物（3-(4-(环戊氧基)苯基)-5-(4-硝基-1-咪唑-2-基)-1,2,4-恶二唑；化合物 ），它对常见的肠道细菌或其他测试的生物体没有活性。化合物 对艰难梭菌具有选择性杀菌作用，作用靶点为细胞壁合成。
