Xiao Zhu-Ping, Wei Wei, Wang Peng-Fei, Shi Wei-Kang, Zhu Na, Xie Me-Qun, Sun Yu-Wen, Li Ling-Xia, Xie Yong-Xiang, Zhu Liang-Song, Tang Nian, Ouyang Hui, Li Xian-Hui, Wang Guang-Cheng, Zhu Hai-Liang
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
Eur J Med Chem. 2015 Sep 18;102:631-8. doi: 10.1016/j.ejmech.2015.08.025. Epub 2015 Aug 14.
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.
酪氨酰 - tRNA合成酶（TyrRS）是细菌蛋白质生物合成中的一种必需酶，是寻找新型抗菌剂的一个有吸引力的治疗靶点，本文已合成了一系列N2 -（芳基乙酰基）甘氨酰苯胺并将其鉴定为TyrRS抑制剂。这些研究产生了几种化合物，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活性最高，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）均表现出优异的活性。与母体骨架3 - 芳基呋喃 - 2(5H)-酮相比，N2 -（芳基乙酰基）甘氨酰苯胺显著提高了对革兰氏阴性菌的效力，表明该骨架在开发新型抗菌药物方面具有巨大潜力。
