Abstract：
In this study, indlomycin, an inhibitor of tryptophanyl-tRNA synthetase (TrpRS), and 29 racemic indolmycin derivatives were synthesized, their antibacterial activity were evaluated against methicillin-resistant Staphylococcus aureus (S. aureus) NRS384, ATCC29213, and Escherichia coli (E. coli) ATCC25922 strains. Compounds (±)-7a, (±)-7b, (±)-7c and (±)-7e exhibited minimum inhibitory concentration (MIC) values of 1-2 μg/mL against S. aureus NRS384 and ATCC29213, exhibiting significant antibacterial activity, but none of the compounds exhibited antibacterial activity against E. coli. To investigate the effect of conformation on antibacterial activity, seven racemic compounds with good antibacterial activity were separated, and the antibacterial activity of these 14 compounds was evaluated on 25 bacterial strains. This revealed that the isomers with natural conformations (1\'R, 5S) had significantly better antibacterial activity than the enantiomeric isomers and racemates. Compounds 7aa, 7ba, 7ca, and 7ea exhibited good antibacterial activity against 21 strains of S. aureus and S. epidermidis with MIC values of 0.125-2 μg/mL, which were superior to that of vancomycin, used in clinical practice. The compounds 7aa, 7ba, 7ca and 7ea were moderately bound to plasma proteins and were stable in the whole blood of CD-1 mice. In conclusion, a series of new indomycin derivatives with stronger antibacterial activity against G+ bacteria were obtained.
摘要：
在这项研究中,吲哚霉素,色氨酸-tRNA合成酶（TrpRS）的抑制剂，合成了29个外消旋吲哚霉素衍生物，对耐甲氧西林金黄色葡萄球菌(S.金黄色葡萄球菌)NRS384、ATCC29213和大肠杆菌(E.大肠杆菌)ATCC25922株。化合物(±)-7a,(±)-7b,（±）-7c和（±）-7e对金黄色葡萄球菌NRS384和ATCC29213表现出1-2μg/mL的最小抑制浓度（MIC）值，表现出明显的抗菌活性，但没有一种化合物对大肠杆菌具有抗菌活性。为了研究构象对抗菌活性的影响，分离出7个具有良好抗菌活性的外消旋化合物,并在25株细菌上评价了这14种化合物的抗菌活性。这表明异构体具有天然构象(1\'R，5S）具有明显优于对映体异构体和外消旋体的抗菌活性。化合物7aa,7ba,7ca,7ea对21株金黄色葡萄球菌和表皮葡萄球菌具有良好的抗菌活性，MIC值为0.125-2μg/mL，优于万古霉素，用于临床实践。化合物7aa,7ba,7ca和7ea与血浆蛋白适度结合并且在CD-1小鼠的全血中稳定。总之,获得了一系列对G细菌具有更强抗菌活性的新吲哚霉素衍生物。
