阿兹屈南
头孢他啶
抗菌活性
肉汤微量稀释
最小抑制浓度
化学
抗菌剂
美罗培南
抗生素
微生物学
细菌
生物
抗生素耐药性
有机化学
生物化学
亚胺培南
铜绿假单胞菌
遗传学
作者
Lijuan Zhai,Lili He,Yuanbai Liu,Ko Ko Myo,Zafar Iqbal,Jian Sun,Jinbo Ji,Jingwen Ji,Yangxiu Mu,Yuanyu Gao,Dong Tang,Haikang Yang,Zhixiang Yang
出处
期刊:Medicinal Chemistry
日期:2022-01-01
卷期号:18 (5): 574-588
标识
DOI:10.2174/1573406417666210830122954
摘要
Mononcyclic β-lactams are regarded as the most resistant class of β-lactams against a series of β-lactamases, although they possess limited antibacterial activity. Aztreonam, being the first clinically approved monobactam, needs broad-spectrum efficacy through structural modification.We strive to synthesize a number of monocyclic β-lactams by varying the substituents at N1, C3, and C4 positions of azetidinone ring and study the antimicrobial effect on variable bacterial strains.Seven new monobactam derivatives 23a-g, containing substituted-amidine moieties linked to the azetidinone ring via thiazole linker, were synthesized through multistep synthesis. The final compounds were investigated for their in vitro antibacterial activities using the broth microdilution method against ten bacterial strains of clinical interest. The minimum inhibitory concentrations (MICs) of newly synthesized derivatives were compared with aztreonam, ceftazidime, and meropenem, existing clinical antibiotics.All compounds 23a-g showed higher antibacterial activities (MIC 0.25 μg/mL to 64 μg/mL) against tested strains as compared to aztreonam (MIC 16 μg/mL to >64 μg/mL) and ceftazidime (MIC >64 μg/mL). However, all compounds, except 23d, exhibited lower antibacterial activity against all tested bacterial strains compared to meropenem.Compound 23d showed comparable or improved antibacterial activity (MIC 0.25 μg/mL to 2 μg/mL) to meropenem (MIC 1 μg/mL to 2 μg/mL) in the case of seven bacterial species. Therefore, compound 23d may be a valuable lead target for further investigations against multi-drug resistant Gram-negative bacteria.
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