对耐甲氧西林金黄色葡萄球菌具有体外和体内效力增强的DNA结合配体。
DNA binding ligands with improved in vitro and in vivo potency against drug-resistant Staphylococcus aureus.
作者信息
Hu Wenhao, Bürli Roland W, Kaizerman Jacob A, Johnson Kirk W, Gross Matthew I, Iwamoto Mari, Jones Peter, Lofland Denene, Difuntorum Stacey, Chen Hsiu, Bozdogan Bülent, Appelbaum Peter C, Moser Heinz E
机构信息
Genesoft Pharmaceuticals, Inc., 7300 Shoreline Court, South San Francisco, California 94080, USA.
出版信息
J Med Chem. 2004 Aug 26;47(18):4352-5. doi: 10.1021/jm049712g.
Potent in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA) has been difficult to achieve with previously reported DNA binding antibacterials. Herein, we describe an efficient access to a focused library of new analogues yielding compounds with improved activity in a mouse peritonitis model. The most potent molecules (14 and 19) exhibit efficacy against MRSA at ED50 values of approximately 1 and approximately 5 mg/kg, respectively, and display excellent in vitro activity against vancomycin-resistant S. aureus.
对于先前报道的DNA结合抗菌药物而言，在体内对耐甲氧西林金黄色葡萄球菌（MRSA）产生强效活性一直难以实现。在此，我们描述了一种高效构建聚焦新类似物文库的方法，该文库产生的化合物在小鼠腹膜炎模型中具有增强的活性。最具活性的分子（14和19）分别在约1mg/kg和约5mg/kg的ED50值下对MRSA表现出疗效，并且对耐万古霉素金黄色葡萄球菌显示出优异的体外活性。
Zotero 插件