Constructing a new antibacterial structural framework is an effective strategy to combat drug resistance. This work discovered a class of naphthalimidopropanediols (NIOLs) as a novel structural type of potential broad-spectrum antibacterial agents. Especially, NIOLs 9u, 12i, 15 against Staphylococcus aureus and NIOLs 9l, 13a against Pseudomonas aeruginosa showed excellent inhibitory activities, and they displayed high membrane selectivity from an electrostatic distinction on the membranes between bacteria and mammalian cells. These highly active NIOLs could effectually inhibit the bacterial growths, and relieve the resistance developments. Moreover, the facts of membrane depolarization, outer/inner membrane permeabilization and leakage of intracellular materials, demonstrated that these NIOLs could target and destroy the S. aureus or P. aeruginosa membranes. In particular, they could disrupt the antioxidant defense systems of S. aureus or P. aeruginosa through up-regulation of reactive oxygen species. Simultaneously, they could render the metabolic inactivation of the tested strains, and eradicate the formed biofilms and efficiently kill the strains within the biofilms. The in vitro and in vivo cytotoxicity assay indicated that these compounds possessed low toxicity. These findings of novel NIOLs as potential broad-spectrum antibacterial members provided a bright hope for conquering drug resistance.

构建新的抗菌结构框架是对抗耐药性的有效策略。这项工作发现了一类萘酰亚胺丙二醇 (NIOL) 作为一种新型结构类型的潜在广谱抗菌剂。特别是针对金黄色葡萄球菌的 NIOLs 9u 、12i、15和针对铜绿假单胞菌的 NIOLs 9l、13a显示出优异的抑制活性，并且它们通过细菌和哺乳动物细胞之间的膜上的静电区别显示出高膜选择性。这些高活性的 NIOL 可以有效地抑制细菌的生长，并缓解耐药性的发展。此外，膜去极化、外膜/内膜透化和细胞内物质渗漏的事实表明，这些 NIOL 可以靶向和破坏金黄色葡萄球菌或铜绿假单胞菌膜。特别是，它们可以破坏金黄色葡萄球菌或铜绿假单胞菌的抗氧化防御系统通过上调活性氧。同时，它们可以使被测菌株代谢失活，根除已形成的生物膜，有效杀死生物膜内的菌株。体外和体内细胞毒性试验表明这些化合物具有低毒性。这些新的NIOLs作为潜在的广谱抗菌成员的发现为克服耐药性提供了光明的希望。