3-Aryl-4-acyloxyethoxyfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: synthesis, molecular docking and antibacterial evaluation.
3-Aryl-4-acyloxyethoxyfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: synthesis, molecular docking and antibacterial evaluation.
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DOI：
10.1016/j.bmc.2013.06.066
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发表时间：
2013-09
影响因子：
3.5
通讯作者：
Xu-dong Wang;Rui-Cheng Deng;Jing-Jun Dong;Zhi-Yun Peng;Xiao-ming Gao;Shu-ting Li;W. Lin;Chun-lei Lu;Zhu-Ping Xiao;Hailiang Zhu
中科院分区：
文献类型：
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作者：
Xu-dong Wang;Rui-Cheng Deng;Jing-Jun Dong;Zhi-Yun Peng;Xiao-ming Gao;Shu-ting Li;W. Lin;Chun-lei Lu;Zhu-Ping Xiao;Hailiang Zhu
设计、合成了38个3-芳基-4-酰氧基乙氧基呋喃-2（5 H）-酮类化合物，并进行了抑菌活性测试。部分化合物对革兰氏阳性菌、革兰氏阴性菌和真菌均有明显的抗菌活性。其中4-（2-（3-氯苯甲酰氧基）乙氧基）-3-（4-氯苯基）呋喃-2（5 H）-酮（d40）对金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌和白色念珠菌的MIC_（50）分别为2.0 μg/mL、4.3 μg/mL、1.5 μg/mL和1.2 μg/mL。结果表明，对全细胞细菌的MIC_（50）值与对酪氨酰-tRNA合成酶的MIC_（50）值呈正相关。同时，将d40与金黄色葡萄球菌tRNA合成酶活性位点进行了分子对接，发现与活性位点紧密匹配的抑制剂可能是其具有较高抑菌活性的重要原因。
Thirty-eight 3-aryl-4-acyloxyethoxyfuran-2(5H)-ones were designed, prepared and tested for antibacterial activities. Some of them showed significant antibacterial activity against Gram-positive organism, Gram-negative organism and fungus. Out of these compounds, 4-(2-(3-chlorophenylformyloxy)ethoxy)-3-(4-chlorophenyl)furan-2(5H)-one (d40) showed the widest spectrum of activity with MIC50of 2.0 μg/mL againstStaphylococcus aureus, 4.3 μg/mL againstEscherichia coli, 1.5 μg/mL againstPseudomonas aeruginosaand 1.2 μg/mL againstCandida albicans. Our data disclosed that MIC50values against whole cell bacteria are positive correlation with MIC50values against tyrosyl-tRNA synthetase. Meanwhile, molecular docking ofd40intoS.aureustyrosyl-tRNA synthetase active site was also performed, and the inhibitor tightly fitting the active site might be an important reason why it has high antimicrobial activity.