A series of novel Schiff base-linked imidazole naphthalimides were developed and their antimicrobial behavior demonstrated that compound 9i could effectively inhibit the growth of some tested strains, especially for MRSA (MIC = 0.003 μmol mL−1), which was superior to the reference drugs. Bacterial membrane permeabilization, bacterial resistance and time-kill kinetic assays of compound 9i against MRSA manifested that it was able to permeate the cell membrane, rapidly kill the tested strains and stall the development of bacterial resistance. Preliminary research revealed that compound 9i could form a stable complex with calf thymus DNA by intercalation mode. These results suggested that compound 9i could serve as a promising anti-MRSA candidate.

N-Alkylated benzimidazole derivatives have been synthesized via the aza-Michael addition reactions of 1H-benzimidazoles to α,β-unsaturated compounds in water and palladium acetate obviously promoted these transformations. The reported method, overcoming the inactivation of palladium under the equivalent nitrogenous conditions, has the advantages of convenient manipulation, atom-economy, as well as environmental friendliness. The bioactive results showed that butyl 3-(5,6-dimethyl-1H-benzo[d]imidazol-1-yl)propanoate (3c) exhibited excellent inhibitory activity against Bacillus subtilis (MIC = 16 μg/mL) and Bacillus proteus (MIC = 8 μg/mL). Therefore, this process would facilitate the construction of various potential bioactive compounds based on the benzimidazole scaffold under mild conditions.N-Alkylated benzimidazole derivatives have been synthesized via the aza-Michael addition reactions of 1H-benzimidazoles to α,β-unsaturated compounds in water and palladium acetate obviously promoted these transformations. The reported method, overcoming the inactivation of palladium under the equivalent nitrogenous conditions, has the advantages of straightforward manipulation, atom-economy, as well as environmental friendliness.

Inter/intramolecular approaches to sp2 C–N bond formation of N-alkenyl benzimidazoles have been accomplished in the presence of an iodide anion associated with a copper catalyst. Both intermolecular and intramolecular reactions included tandem processes, in which selective iodination of sp3 C–H bond at the α-position of ester under mild conditions was demonstrated for the first time. Tandem reactions involving sp3 C–H activation via α-iodo ester intermediate under copper catalysis efficiently provided more than 20 novel azole compounds, and free radicals were not involved in this transformation.

A novel series of benzimidazole derived naphthalimide triazoles and some corresponding triazoliums have been successfully synthesized and characterized by 1H NMR, 13C NMR, 1H-1H COSY, IR and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by two-fold serial dilution. 2-Chlorobenzyl triazolium 8g and compound 9b with octyl group exhibited the best antibacterial activities among all the tested compounds, especially against S. aureus with inhibitory concentration of 2 μg/mL which was equipotent potency to Norfloxacin (MIC=2 μg/mL) and more active than Chloromycin (MIC=7 μg/mL). Triazoliums 8g and 8f bearing 3-fluorobenzyl moiety displayed the best antifungal activities (MIC=2−19 μg/mL) against all the tested fungal strains without being toxic to PC12 cell line within concentration of 128 μg/mL. Further investigations by fluorescence and UV-Vis spectroscopic methods revealed that the compound 8g could effectively intercalate into calf thymus DNA to form the 8g-DNA complex which could block DNA replication, exerting powerful antimicrobial activities.

A series of novel coumarinazoles were designed, synthesized, and characterized by IR, NMR, MS and HRMS spectra. The bioactive assay for the newly prepared compounds against six bacteria and five fungi manifested that most new compounds exhibited good or even stronger antibacterial and antifungal activities in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. Bis-azole alcohols 7a and 7d–e showed better anti-Candida utilis activity than mono-azole derivatives 4a and 4d–e at the tested concentrations, and they were more potent than the clinical Fluconazole. While triazole alcohol 7a gave comparable anti-Candida albicans and anti-Candida mycoderma activity to Fluconazole and better anti-MRSA activity than mono-triazole one 4a and clinical Norfloxacin. 1H-Benzoimidazol-2-ylthio coumarin derivatives 4e and 7e gave the strongest anti-Escherichia coli JM109 efficacy. Oxiran-2-ylmethoxy moiety was found to be a beneficial fragment to improve antibacterial and antifungal activity to some extent.Figure optionsDownload full-size imageDownload high-quality image (127 K)Download as PowerPoint slide

A unique one-pot reaction via CC cleavage from aminomethylene benzimidazoles with commercial halides to access novel benzimidazolones is reported for the first time. The previously unexploited transformation is able to perform smoothly in the presence of commercial potassium carbonate, while the stronger inorganic bases or organic amines as catalysts are not favorable to the transformation. Significant influential factors including base, temperature, solvent, water content, and molar ratio of substrates to this reaction are investigated, and possibly mechanistic consideration is also discussed. Some synthesized benzimidazolones were evaluated and exhibited better bioactivities against tested strains than clinical drugs chloromycin, norfloxacin, and fluconazole.