一种新型质子载体对耐甲氧西林金黄色葡萄球菌的活性。
Activity of a novel protonophore against methicillin-resistant Staphylococcus aureus.
作者信息
Tharmalingam Nagendran, Jayamani Elamparithi, Rajamuthiah Rajmohan, Castillo Dawilmer, Fuchs Beth Burgwyn, Kelso Michael J, Mylonakis Eleftherios
机构信息
Infectious Diseases Division, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
出版信息
Future Med Chem. 2017 Aug;9(12):1401-1411. doi: 10.4155/fmc-2017-0047. Epub 2017 Aug 3.
AIM
Compound 1-(4-chlorophenyl)-4,4,4-trifluoro-3-hydroxy-2-buten-1-one (compound 1) was identified as a hit against methicillin-resistant Staphylococcus aureus (MRSA) strain MW2.
METHODS & RESULTS: The MIC of compound 1 against MRSA was 4 μg/ml. The compound showed enhanced activity at acidic pH by lowering bacterial intracellular pH and exhibited no lysis of human red blood cells at up to 64 μg/ml and its IC against HepG2 cells was 32 μg/ml. The compound reduced 1-log colony forming units of intracellular MRSA in macrophages and prolonged the survival of MRSA-infected Caenorhabditis elegans (p = 0.0015) and Galleria mellonella (p = 0.0002).
CONCLUSION
Compound 1 is a protonophore with potent in vitro and in vivo activity against MRSA and no toxicity in mammalian cells up to 8 μg/ml that warrants further investigation as a novel antibacterial.
目的
化合物1-（4-氯苯基）-4,4,4-三氟-3-羟基-2-丁烯-1-酮（化合物1）被鉴定为对耐甲氧西林金黄色葡萄球菌（MRSA）菌株MW2有活性的先导化合物。
方法与结果
化合物1对MRSA的最低抑菌浓度（MIC）为4μg/ml。该化合物通过降低细菌细胞内pH值在酸性pH条件下显示出增强的活性，在高达64μg/ml时对人红细胞无裂解作用，其对HepG2细胞的半数抑制浓度（IC）为32μg/ml。该化合物减少了巨噬细胞内MRSA 1个对数的菌落形成单位，并延长了感染MRSA的秀丽隐杆线虫（p = 0.0015）和大蜡螟（p = 0.0002）的存活时间。
结论
化合物1是一种质子载体，对MRSA具有强大的体外和体内活性，在高达8μg/ml时对哺乳动物细胞无毒性，作为一种新型抗菌剂值得进一步研究。
Zotero 插件