Increasing rates of bacterial resistance to known classes of antibiotics present a severe global challenge. As a consequence, the search for new chemical entities that address novel bacterial targets remains ongoing. Aminoacyl-tRNA synthetases (aaRS) catalyze the ligation of amino acids to their cognate tRNAs and they are essential for protein synthesis. Inhibition of aaRS leads to protein synthesis inhibition, which cause cell growth arrest. Consequently, aminoacyl-tRNA synthetase is a class of potential anti-infective target. AaRS inhibitors identified from natural products and their derivatives, substrate and reaction intermediate mimics, synthetic compounds and hits of virtual screening as novel antibacterial and antifungal agents are summarized in this article. The target characteristic, classification and catalytic mechanism of aminoacyl-tRNA synthetases are also introduced.%细菌耐药性的不断上升对现有阶段的抗生素类药物提出了一个严峻的挑战,同时也掀起了针对于新靶标的抗菌药物的研究.氨酰tRNA合成酶(aaRS)催化特定氨基酸连接到相应的tRNA分子上,在蛋白质的合成过程中起着必不可少的作用.氨酰tRNA合成酶的抑制会导致蛋白质合成的停止,扰乱细菌和真菌的生长,因此氨酰tRNA合成酶是一类潜在的抗感染靶标.本文分别综述了天然产物及其衍生的aaRS抑制剂,底物和反应中间体模拟物,通过合成和通过虚拟筛选得到的aaRS抑制剂作为新型抗细菌和抗真菌药物的研究进展,并对aaRS的靶标特点、分类和催化机制作一简要介绍.
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