Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F5a and its derivatives
Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F5a and its derivatives
复制标题
阿扎霉素 F5a 及其衍生物的抗甲氧西林金黄色葡萄球菌测定
DOI：
10.1016/s1875-5364(14)60061-3
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发表时间：
2014-04-01
影响因子：
4.6
通讯作者：
Pei Ying
中科院分区：
文献类型：
--
作者：
Yuan Gan-Jun;Li Pei-Bo;Pei Ying
目的：目的：寻找抗耐甲氧西林金黄色葡萄球菌（MRSA）的微生物天然产物或其衍生物。在烃基醇-AcOH（4：1）体系中进行β-羟丙基化反应，然后在甲醇-水（7：3）体系中用2 mol·L ~（-1）KOH进行脱丙二酰化反应，合成了azalomyceticus及其衍生物。用琼脂扩散法和微量肉汤稀释法测定了它们对MRSA ATCC 33592和3株MRSA临床分离株的抗菌活性。抗MRSA活性测定结果表明，化合物1 ~ 5对MRSA具有显著的抑制活性，其最小抑菌浓度（MIC）分别为3.0-4.0、0.5-1.0、0.67-1.0、0.67-0.83和0.5-0.83 μ g·mL（-1）。阿扎霉素F-5a及其衍生物2-5具有明显的抗MRSA活性，其中2 - 5的抗MRSA活性高于1，而2 - 5的抗MRSA活性无明显差异。还显示阿扎霉素F-5a的丙二酰单酯基团对其抗MRSA活性不太重要。
AIM: To discover anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) microbial natural products or their derivatives.METHOD: Azalomycin F-5a (1) was prepared through fermentation of Streptomyces hygroscopicus var. azalomyceticus, and its derivatives were synthesized through hydrocarbylation in hydrocarbyl alcoholic-AcOH (4: 1) and subsequent demalonylation with 2 mol-L-1 KOH in MeOH-H2O (7 : 3). Their activities against MRSA ATCC 33592 and three clinical MRSA isolates were evaluated by the agar diffusion and broth microdilution methods.RESULTS: Four demalonylazalomycin F-5a derivatives 2 to 5 were synthesized. The anti-MRSA activity assay indicated that compounds 1 to 5 showed remarkable activity against MRSA, and their minimum inhibitory concentrations (MICs) were respectively 3.0-4.0, 0.5-1.0, 0.67-1.0, 0.67-0.83, and 0.5-0.83 mu g.mL(-1).CONCLUSION: Azalomycin F-5a and the demalonylazalomycin F-5a derivatives 2-5 showed remarkable anti-MRSA activity, and the anti-MRSA activities of 2 to 5 were higher than that of 1, while the anti-MRSA activities of 2 to 5 showed no obvious differences. It was also shown that the malonyl monoester group of azalomycin F-5a was less important for its anti-MRSA activity.