7189-18-6Relevant articles and documents
Design, Synthesis and Antimicrobial Evaluation of Novel Benzimidazole-incorporated Naphthalimide Derivatives as Salmonella typhimurium DNA Intercalators, and Combination Researches
Ning, Zhi-Wei,Zhang, Hui-Zhen,Zhou, cheng-He
, p. 544 - 557 (2022/03/09)
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 10g bearing a 2,4-dichlorobenzyl moiety exhibited the best antimicrobial activities in this series relatively; especially, it exhibited comparable activity against Salmonella typhi-murium in comparison with the reference drug Norfloxacin (MIC = 4 μg/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 hex-amer duplex by π–π 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 benzimidaz-ole-incorporated naphthalimide derivatives as potent antimicrobial agents.
Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove
Wang, Ya-Nan,Bheemanaboina, Rammohan R. Yadav,Cai, Gui-Xin,Zhou, Cheng-He
, p. 1621 - 1628 (2018/03/29)
A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus (MIC = 4 μg/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c–DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity.
DEUTERIUM MODIFIED BENZIMIDAZOLES
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Page/Page column 30-31, (2010/12/17)
This invention relates to derivatives of 1-(p-chIorobenzyI)-2-(1-pyrrolidinylmethyl)benzimidazole according to Formula I wherein at least one Y is deuterium described herein and pharmaceutically acceptable salts thereof. This invention also provides compo
