College of Chemistry and Chemical Engineering, Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou, PR China.
Bioorg Med Chem. 2011 Mar 1;19(5):1571-9. doi: 10.1016/j.bmc.2011.01.051. Epub 2011 Feb 1.
Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of these compounds, 3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one (4a11) showed the most potent antibacterial activity against S. aureus ATCC 25923 with MIC(50) of 0.42 μg/mL. The enzyme assay revealed that the possible antibacterial mechanism of the synthetic compounds might be due to their inhibitory activity against tyrosyl-tRNA synthetase. Molecular dockings of 4a11 into S. aureus tyrosyl-tRNA synthetase active site were also performed. This inhibitor snugly fitting the active site might well explain its excellent inhibitory activity. Meanwhile, this modeling disclosed that a more suitable optimization strategy might be to modify the benzene ring at 3-position of furanone with hydrophilic groups.
设计、合成了 31 个 3-芳基-4-烷基氨基-2（5H）-呋喃酮，并对其进行了抗菌活性测试。部分化合物对革兰氏阳性菌，尤其是金黄色葡萄球菌 ATCC 25923 表现出显著的抗菌活性，但对革兰氏阴性菌均无活性。在这些化合物中，3-(4-溴苯基）-4-(2-(4-硝基苯基）腙基）-2（5H）-呋喃酮（4a11）对金黄色葡萄球菌 ATCC 25923 的抗菌活性最强，MIC（50）为 0.42 μg/mL。酶活性测定表明，合成化合物的可能抗菌机制可能是由于其对酪氨酸-tRNA 合成酶的抑制活性。还对 4a11 与金黄色葡萄球菌酪氨酸-tRNA 合成酶活性位点进行了分子对接。该抑制剂与活性位点紧密结合，很好地解释了其优异的抑制活性。同时，该模型揭示了更合适的优化策略可能是用亲水基团修饰呋喃酮 3-位上的苯环。
