新型含腙基的联苯恶唑烷酮类似物的合成及抗菌活性评价作为有前途的抗菌剂。
Synthesis and antibacterial activity evaluation of novel biaryloxazolidinone analogues containing a hydrazone moiety as promising antibacterial agents.
机构信息
Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, 103 Wenhua Road, Shenhe District, Shenyang, 110016, PR China.
Department of Clinical Laboratory, The 309th Hospital of Chinese People's Liberation Army, Beijing, 100091, China.
出版信息
Eur J Med Chem. 2018 Oct 5;158:247-258. doi: 10.1016/j.ejmech.2018.09.004. Epub 2018 Sep 5.
A series of linezolid analogues containing a hydrazone moiety were designed, synthesized and evaluated for their antibacterial activity. Most compounds exhibited more potent antibacterial activity against S.aureus, MRSA, MSSA, LREF and VRE pathogens as compared with linezolid and radezolid. Compounds 9a, 9c, 9f, 9g, 10m and 10t were more potent against tested clinical isolates of MRSA, MSSA, VRE and LREF as compared to linezolid. Compound 9a exhibited comparable activity with linezolid against human MAO-A for safety evaluation and showed moderate metabolism in human liver microsome. The most promising compound 9a showed remarkable antibacterial activity against S.aureus, MRSA, MSSA, LREF and VRE pathogens with MIC value of 0.0675 mg/mL, respectively, which was 15- to 30-fold more potent than linezolid.
设计、合成了一系列含有腙部分的利奈唑胺类似物，并对其抗菌活性进行了评价。与利奈唑胺和雷迪唑胺相比，大多数化合物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌、甲氧西林敏感金黄色葡萄球菌、利奈唑胺耐药表皮葡萄球菌和万古霉素耐药肠球菌等病原体表现出更强的抗菌活性。化合物 9a、9c、9f、9g、10m 和 10t 对测试的耐甲氧西林金黄色葡萄球菌、甲氧西林敏感金黄色葡萄球菌、万古霉素耐药肠球菌和利奈唑胺耐药表皮葡萄球菌临床分离株的活性均强于利奈唑胺。化合物 9a 对人 MAO-A 的活性与利奈唑胺相当，可用于安全性评价，并且在人肝微粒体中显示出中等代谢活性。最有前途的化合物 9a 对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌、甲氧西林敏感金黄色葡萄球菌、利奈唑胺耐药表皮葡萄球菌和万古霉素耐药肠球菌等病原体表现出显著的抗菌活性，MIC 值分别为 0.0675mg/mL，分别比利奈唑胺强 15-30 倍。
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