Novel naphthalimide nitroimidazoles as multitargeting antibacterial agents against resistant Acinetobacter baumannii

作者：Kang, Jie; Gopala, Lavanya; Tangadanchu, Vijai Kumar Reddy; Gao, Wei-Wei; Zhou, Cheng-He^*

来源：Future Medicinal Chemistry, 2018, 10(7): 711-724.

DOI：10.4155/fmc-2017-0160

• antibacterial
• naphthalimide
• nitroimidazole
• resistant A. baumannii

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 mu mol/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. @@@ [GRAPHICS] @@@ .

• 出版日期2018-4
• 单位西南大学