Medicinal chemistry (Shariqah (United Arab Emirates)) | 2021
Design, Synthesis and Antimicrobial Evaluation of Novel Benzimidazole-incorporated Naphthalimide Derivatives As Salmonella typhimurium DNA Intercalators, and Combination Researches.
Abstract
OBJECTIVE\nA series of novel benzimidazole-incorporated naphthalimide derivatives were designed and prepared to overcome the increasing antibiotic resistance.\n\n\nMETHOD\nThe 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 typhimurium DNA was studied using UV-vis spectroscopic methods.\n\n\nRESULTS\nCompound 10g bearing a 2,4-dichlorobenzyl moiety exhibited the best antimicrobial activities in this series relatively, especially it gave the comparable action against Salmonella typhimurium compared to the reference drug Norfloxacin (MIC = 4 mg/mL). Further research showed that compound 10g could effectively intercalate into the Salmonella typhimurium DNA to form the 10g-DNA complex, which might correlate with the inhibitory activity. Molecular docking results demonstrated that naphthalimide compound 10g could interact with base-pairs of DNA hexamer duplex by p-p stacking. Additionally, the combinations of the solid active combination with clinical drugs gave better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separated use alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive M. ruber.\n\n\nCONCLUSION\nThis work opened up a good starting point to optimize the structures of benzimidazole-incorporated naphthalimide derivatives as potent antimicrobial agents.