کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1359106 | 981384 | 2010 | 18 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: High-throughput identification of antibacterials against methicillin-resistant Staphylococcus aureus (MRSA) and the transglycosylase High-throughput identification of antibacterials against methicillin-resistant Staphylococcus aureus (MRSA) and the transglycosylase](/preview/png/1359106.png)
To identify new transglycosylase inhibitors with potent anti-methicillin-resistant Staphylococcusaureus (MRSA) activities, a high-throughput screening against Staphylococcusaureus was conducted to look for antibacterial cores in our 2 M compound library that consists of natural products, proprietary collection, and synthetic molecules. About 3600 hits were identified from the primary screening and the subsequent confirmation resulted in a total of 252 compounds in 84 clusters which showed anti-MRSA activities with MIC values as low as 0.1 μg/ml. Subsequent screening targeting bacterial transglycosylase identified a salicylanilide-based core that inhibited the lipid II polymerization and the moenomycin-binding activities of transglycosylase. Among the collected analogues, potent inhibitors with the IC50 values below 10 μM against transglycosylase were identified. The non-carbonhydrate scaffold reported in this study suggests a new direction for development of bacterial transglycosylase inhibitors.
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Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 24, 15 December 2010, Pages 8512–8529