新型萘酰亚胺硝咪唑类化合物作为抗耐药鲍曼不动杆菌的多靶抗菌剂。
Novel naphthalimide nitroimidazoles as multitargeting antibacterial agents against resistant Acinetobacter baumannii.
机构信息
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Southwest University, Chongqing 400715, PR China.
出版信息
Future Med Chem. 2018 Apr 1;10(7):711-724. doi: 10.4155/fmc-2017-0160. Epub 2018 Apr 19.
AIM
The increasing emergence of resistant bacteria imposed an urgent request to discover novel antibacterial agents. This work was to develop naphthalimide nitroimidazoles as potentially antibacterial agents. Results/methodology: Compound 9e showed the strong antibacterial activity (minimal inhibitory concentration = 0.013 μmol/ml) against resistant Acinetobacter baumannii (A. baumannii) with rapid killing effect and no obvious triggering of the development of resistance. Its combination use with chloromycin, norfloxacin or clinafloxacin improved the antibacterial potency. It could not only effectively permeate membrane of resistant A. baumannii bacteria, but also intercalate into resistant A. baumannii DNA to form 9e-DNA complex. The interaction with bacterial DNA gyrase B was driven by hydrogen bonds.
CONCLUSION
Compound 9e should be a potentially multitargeting antibacterial agent against resistant A. baumannii.
目的
耐药菌的不断出现对新型抗菌药物提出了迫切需求。本研究旨在开发萘酰亚胺类硝基咪唑类化合物作为具有潜在抗菌活性的药物。
结果/方法：化合物 9e 对耐药鲍曼不动杆菌（A.baumannii）具有较强的抗菌活性（最小抑菌浓度=0.013μmol/ml），具有快速杀菌作用，且不易引发耐药性。与氯霉索、诺氟沙星或克林沙星联合使用可提高抗菌活性。它不仅能有效穿透耐药鲍曼不动杆菌的细胞膜，还能插入耐药鲍曼不动杆菌 DNA 中形成 9e-DNA 复合物。与细菌 DNA 回旋酶 B 的相互作用是由氢键驱动的。
结论
化合物 9e 可能是一种针对耐药鲍曼不动杆菌的多靶抗菌药物。
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