7191-71-1Relevant 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.
Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug-Resistant Pseudomonas aeruginosa DNA
Wang, Ya-Nan,Bheemanaboina, Rammohan R. Yadav,Gao, Wei-Wei,Kang, Jie,Cai, Gui-Xin,Zhou, Cheng-He
, p. 1004 - 1017 (2018/04/30)
A series of benzimidazole–quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2-fluorobenzyl derivative 5 b (ethyl 7-chloro-6-fluoro-1-[[1-[(2-fluorophenyl)methyl]benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep-2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV–DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b. Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug-resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.
Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents
Zhang, Ling,Addla, Dinesh,Ponmani, Jeyakkumar,Wang, Ao,Xie, Dan,Wang, Ya-Nan,Zhang, Shao-Lin,Geng, Rong-Xia,Cai, Gui-Xin,Zhou, Cheng-He,Li, Shuo
, p. 160 - 182 (2018/05/17)
A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.
