Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold
Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold
复制标题
基于N2-(芳基乙酰基)甘氨酰苯胺支架的新型抗菌剂酪氨酰-tRNA合成酶抑制剂的合成与评价
DOI：
10.1016/j.ejmech.2015.08.025
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发表时间：
2015-09-18
影响因子：
6.7
通讯作者：
Zhu, Hai-Liang
中科院分区：
文献类型：
--
作者：
Xiao, Zhu-Ping;Wei, Wei;Zhu, Hai-Liang
酪氨酰-tRNA合成酶(Tyrosyl-tRNA Synthetase，TyrRS)是细菌蛋白质生物合成的关键酶，是寻找新型抗菌药物的理想靶点，本论文合成了一系列N_2-(芳基乙酰基)甘氨酰胺类化合物，并鉴定为TyrRS抑制剂。这些努力产生了几种化合物，对金黄色葡萄球菌的TyrRS的IC50在低微摩尔范围内。在所获得的化合物中，3AP的活性最强，对革兰氏阳性菌(金黄色葡萄球菌)和革兰氏阴性菌(大肠杆菌和铜绿假单胞菌)都表现出良好的活性。与母体支架3-芳基呋喃-2(5H)-酮相比，N-(芳基乙酰基)甘氨酰苯胺对革兰氏阴性杆菌的抗菌活性显著提高，表明该支架具有开发新型抗菌药物的巨大潜力。(C)2015年爱思唯尔·马森公司。版权所有。
Tyrosyl-tRNA synthetase (TyrRS), an essential enzyme in bacterial protein biosynthesis, is an attractive therapeutic target for finding novel antibacterial agents, and a series of N2-(arylacetyl)glycinanilides has been herein synthesized and identified as TyrRS inhibitors. These efforts yielded several compounds, with IC50 in the low micromolar range against TyrRS from Staphylococcus aureus. Out of the obtained compounds, 3ap is the most active and exhibits excellent activity against both Gram-positive (S. aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. In comparison with the parent scaffold 3-arylfuran-2(5H)-one, N2-(arylacetyl)glycinanilide significantly improved the potency against Gram-negative bacterial strains, indicating that this scaffold offers a significant potential for developing new antibacterial drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.