Anti-bacterial and Anti-biofilm Evaluation of Thiazolopyrimidinone Derivatives Targeting the Histidine Kinase YycG Protein of Staphylococcus epidermidis.
Anti-bacterial and Anti-biofilm Evaluation of Thiazolopyrimidinone Derivatives Targeting the Histidine Kinase YycG Protein of Staphylococcus epidermidis.
复制标题
靶向表皮葡萄球菌组氨酸激酶 YycG 蛋白的噻唑并嘧啶酮衍生物的抗菌和抗生物膜评价
DOI：
10.3389/fmicb.2017.00549
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发表时间：
2017
影响因子：
5.2
通讯作者：
Qu D
中科院分区：
文献类型：
--
作者：
Lv Z;Zhao D;Chang J;Liu H;Wang X;Zheng J;Huang R;Lin Z;Shang Y;Ye L;Wu Y;Han S;Qu D
表皮葡萄球菌是医院感染中最重要的条件致病菌之一。主要致病力与S.表皮炎涉及在植入的医疗装置上形成生物膜，生物膜显著降低常规抗生素和宿主免疫系统的功效。这强调了迫切需要设计新的抗葡萄球菌生物膜剂。基于化合物5靶向S. epidermidis YycG，对葡萄球菌具有杀菌活性，设计了39个噻唑并嘧啶酮结构完整的化合物5的衍生物，并对其中7个衍生物进行了进一步筛选，以探讨其抗菌和抗生物膜活性。这7种衍生物对S.表皮葡萄球菌和金黄色葡萄球菌的最小抑菌浓度范围为1.56-6.25 μM。所有衍生物均降低了成熟生物膜中活细胞的比例。它们对哺乳动物细胞的细胞毒性均较低，对人红细胞无溶血性。在剪切力作用下进一步研究了4个衍生物（H5-32、H5-33、H5-34和H5-35）的生物膜抑制活性，结果表明它们均能显著降低S.表皮这些结果表明，化合物5的七种衍生物具有开发成用于根除生物膜相关感染的药剂的潜力。
Staphylococcus epidermidis is one of the most important opportunistic pathogens in nosocomial infections. The main pathogenicity associated with S. epidermidis involves the formation of biofilms on implanted medical devices, biofilms dramatically decrease the efficacy of conventional antibiotics and the host immune system. This emphasizes the urgent need for designing novel anti-staphylococcal biofilm agents. Based on the findings that compound 5, targeting the histidine kinase domain of S. epidermidis YycG, possessed bactericidal activity against staphylococci, 39 derivatives of compound 5 with intact thiazolopyrimidinone core structures were newly designed, 7 derivatives were further screened to explore their anti-bacterial and anti-biofilm activities. The seven derivatives strongly inhibited the growth of S. epidermidis and Staphylococcus aureus in the minimal inhibitory concentration range of 1.56–6.25 μM. All the derivatives reduced the proportion of viable cells in mature biofilms. They all displayed low cytotoxicity on mammalian cells and were not hemolytic to human erythrocytes. The biofilm inhibition activities of four derivatives (H5-32, H5-33, H5-34, and H5-35) were further investigated under shearing forces, they all led to significant decreases in the biofilm formation of S. epidermidis. These results were suggestive that the seven derivatives of compound 5 have the potential to be developed into agents for eradicating biofilm-associated infections.