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鉴定抗金黄色葡萄球菌和奇异变形杆菌的小分子化合物。

Identification of small molecule compounds active against Staphylococcus aureus and Proteus mirabilis.

机构信息

Institute of Immunology and Experimental Therapy of the Polish Academy of Science, Department of Immunology of Infectious Diseases, ul. R. Weigla 12, 53-114, Wroclaw, Poland.

Institute of Immunology and Experimental Therapy of the Polish Academy of Science, Department of Immunology of Infectious Diseases, ul. R. Weigla 12, 53-114, Wroclaw, Poland.

出版信息

Biochem Biophys Res Commun. 2018 Dec 2;506(4):1047-1051. doi: 10.1016/j.bbrc.2018.10.189. Epub 2018 Nov 5.

Abstract

Staphylococcus aureus is a human pathogen rapidly becoming a serious health problem due to ease of acquiring antibiotic resistance. To help identify potential new drug candidates effective against the pathogen, a small focused library was screened for inhibition of bacterial growth against several pathogens, including S. aureus. At least one of the compounds, Compound 10, was capable of blocking bacterial growth of S. aureus in a test tube with IC = 140 ± 30 μM. Another inhibitor, Compound 7, was bacteriostatic against S. aureus with IC ranging from 33 to 150 μM against 3 different strains. However, only Compound 7 was bactericidal against P. mirabilis as examined by electron microscopy. Human cell line toxicity studies suggested that both compounds had small effect on cell growth at 100 μM concentration as examined by MTT assay. Analysis of compounds' structures showed lack of similarity to any known antibiotics and bacteriostatics, potentially offering the inhibitors as an alternative to existing solutions in controlling bacterial infections for selected pathogens.

摘要

金黄色葡萄球菌是一种人类病原体,由于易于获得抗生素耐药性,它正迅速成为一个严重的健康问题。为了帮助识别针对病原体的潜在新药物候选物,对一个小型的、重点突出的文库进行了筛选,以抑制几种病原体的细菌生长,包括金黄色葡萄球菌。至少有一种化合物,即化合物 10,在试管中能够以 IC=140±30μM 的浓度抑制金黄色葡萄球菌的生长。另一种抑制剂,化合物 7,对金黄色葡萄球菌具有抑菌作用,IC 范围为 33 至 150μM,针对 3 种不同的菌株。然而,只有化合物 7 对粘质沙雷氏菌具有杀菌作用,这一点通过电子显微镜检查得到了证实。人细胞系毒性研究表明,在 MTT 测定中,两种化合物在 100μM 浓度下对细胞生长的影响很小。对化合物结构的分析表明,它们与任何已知的抗生素和抑菌剂都没有相似之处,这为控制特定病原体的细菌感染提供了一种替代现有解决方案的潜在抑制剂。

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