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阳离子蒽醌类似物作为选择性抗菌剂

Cationic Anthraquinone Analogs as Selective Antimicrobials.

作者信息

Subedi Yagya Prasad, Chang Cheng-Wei Tom

机构信息

Department of Chemistry & Biochemistry, Utah State University, Logan, UT, USA.

出版信息

Microbiol Insights. 2019 May 20;12:1178636119847809. doi: 10.1177/1178636119847809. eCollection 2019.

Abstract

Development of new antibiotics is always needed in the fight against growing threat from multiple drug-resistant bacteria, such as resistant Gram-negative (G-) and . While the development of broad-spectrum antibiotics has attracted great attention, careful administration of these antibiotics is important to avoid adverse effects, like infection (CDI). The use of broad-spectrum antibiotics, for example, quinolones, can increase the risk of CDI by eradicating the protective bacteria in intestine and encouraging spore germination. Many common intestine bacteria are G- or anaerobic, including , and . Hence, it may be advantageous in certain therapeutic practices to employ selective antimicrobials. For instance, Gram-positive (G+) methicillin-resistant (MRSA) that can cause life-threatening sepsis can be controlled with the use of selective antibiotic, vancomycin. Nevertheless, its effectiveness has been limited with the emerging of vancomycin-resistant (VRSA). A recent report on antimicrobial cationic anthraquinone analogs (CAAs) that show tunable activity and selectivity may provide new hope in the search for selective antimicrobials. In particular, the lead CAA displays prominent activity against MRSA while manifesting low activity against and low cytotoxicity toward normal mammalian cells.

摘要

在应对多重耐药细菌(如耐药革兰氏阴性菌)日益增长的威胁时,始终需要开发新的抗生素。虽然广谱抗生素的开发备受关注,但谨慎使用这些抗生素对于避免不良反应(如艰难梭菌感染,CDI)很重要。例如,使用喹诺酮类等广谱抗生素会通过根除肠道中的保护性细菌并促进艰难梭菌孢子萌发而增加CDI风险。许多常见的肠道细菌是革兰氏阴性菌或厌氧菌,包括艰难梭菌等。因此,在某些治疗实践中使用选择性抗菌药物可能具有优势。例如,可导致危及生命的败血症的耐甲氧西林金黄色葡萄球菌(MRSA)可用选择性抗生素万古霉素进行控制。然而,随着耐万古霉素金黄色葡萄球菌(VRSA)的出现,其有效性受到了限制。最近一份关于显示出可调节活性和选择性的抗菌阳离子蒽醌类似物(CAA)的报告可能为寻找选择性抗菌药物提供新的希望。特别是,先导CAA对MRSA表现出显著活性,而对艰难梭菌活性较低且对正常哺乳动物细胞的细胞毒性较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff2d/6537284/8419864c7c3d/10.1177_1178636119847809-fig1.jpg

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