摘要 : Objective: A series of novel benzimidazole-incorporated naphthalimide derivatives were designed and prepared in an effort to overcome the increasing antibiotic resistance. Methods: The target novel benzimidazole-incorporated napht... 展开 Objective: A series of novel benzimidazole-incorporated naphthalimide derivatives were designed and prepared in an effort to overcome the increasing antibiotic resistance. Methods: The target novel benzimidazole-incorporated naphthalimide derivatives were synthesized from commercial 4-bromo-1,8-naphthalic anhydride and o-phenylene diamine by aminolysis, N-alkylation and so on. The antimicrobial activity of the synthesized compounds was evaluated in vitro by a two-fold serial dilution technique. The interaction of compound 10g with Salmonella typhimuri- um DNA was studied using UV-vis spectroscopic methods. Results: Compound lOg bearing a 2,4-dichlorobenzyl moiety exhibited the best antimicrobial activities in this series relatively; especially, it exhibited comparable activity against Salmonella typhimurium in comparison with the reference drug Norfloxacin (MIC = 4 mu g/mL). Further research showed that compound 10g could effectively intercalate into the Salmonella typhimurium DNA to poi. form the 10g-DNA complex, which might correlate with the inhibitory activity. Molecular docking results demonstrated that naphthalimide compound lOg could interact with base-pairs of DNA hex- amer duplex by pi-pi stacking. Additionally, the combination of the strong active compound with clinical drugs exhibited better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separate use of them alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive M. ruber. Conclusion: This work provides a promising starting point to optimize the structures of benzimidazole-incorporated naphthalimide derivatives as potent antimicrobial agents. 收起