A series of berberine derivatives were synthesized by introducing substituted benzyl groups at C-9.All these synthesized compounds(4a–4m)were screened for their in vitro antibacterial activity against four Gram-posit...A series of berberine derivatives were synthesized by introducing substituted benzyl groups at C-9.All these synthesized compounds(4a–4m)were screened for their in vitro antibacterial activity against four Gram-positive bacteria and four Gram-negative bacteria and evaluated for their antifungal activity against three pathogenic fungal strains.All these compounds displayed good antibacterial and antifungal activities,compared to reference drugs including Ciprofloxacin and Fluconazole;Compounds 4f,4g,and 4l showed the highest antibacterial and antifungal activities.Moreover,all the synthesized compounds were docked into topoisomerase II-DNA complex,which is a crucial drug target for the treatment of microbial infections.Docking results showed that H-bond,π-πstacked,π-cationic,andπ-anionic interactions were responsible for the strong binding of the compounds with the target protein-DNA complex.展开更多
A series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and char- acterized by ^1H NMR, ^13C NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target com- ...A series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and char- acterized by ^1H NMR, ^13C NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target com- pounds gave moderate to good antibacterial and antifungal activities. The N- 1 derived benzotriazole 5e and N-2 de- rived benzotriazole 6a exhibited valuable inhibitory efficacy against some tested strains. Especially, derivative 6a gave superior antifungal efficacies against C. utilis, S. cerevisiae and A. flavus （MIC^0.01, 0.02, 0.02 gmol/mL, respectively） to Fluconazole. The drug combination of compound 5e or 6a with antibacterial Chloromycin, Nor- floxacin and antifungal Fluconazole respectively showed stronger antimicrobial efficiency with less dosage and broader antimicrobial spectrum than their separated use alone. The preliminary interaction with calf thymus DNA revealed that compound 6a could intercalate into DNA to form 6a-DNA supramolecular complex which might be a factor to exert its powerful bioactivity. Molecular docking study indicated strong binding of compound 6a with DNA gyrase. The structural parameters such as molecular orbital energy and molecular electrostatic potential of compound 6a were also investigated, which provided better understanding for its good antimicrobial activity.展开更多
基金supported by the Graduate Students Scientific Research Innovation Projects of Jiangsu Province(No.CXZZ11-0804)Students Training Innovation Program of China Pharmaceutical University(201810316155)
文摘A series of berberine derivatives were synthesized by introducing substituted benzyl groups at C-9.All these synthesized compounds(4a–4m)were screened for their in vitro antibacterial activity against four Gram-positive bacteria and four Gram-negative bacteria and evaluated for their antifungal activity against three pathogenic fungal strains.All these compounds displayed good antibacterial and antifungal activities,compared to reference drugs including Ciprofloxacin and Fluconazole;Compounds 4f,4g,and 4l showed the highest antibacterial and antifungal activities.Moreover,all the synthesized compounds were docked into topoisomerase II-DNA complex,which is a crucial drug target for the treatment of microbial infections.Docking results showed that H-bond,π-πstacked,π-cationic,andπ-anionic interactions were responsible for the strong binding of the compounds with the target protein-DNA complex.
基金This work was partially supported by the National Natural Science Foundation of China [（Nos. 21372186, 21672173）, the Research Fund for International Young Scientists from International （Regional） Cooperation and Exchange Program （No. 81650110529）] and Chongqing Special Foundation for Postdoctoral Research Proposal （Xm2015031 ）.
文摘A series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and char- acterized by ^1H NMR, ^13C NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target com- pounds gave moderate to good antibacterial and antifungal activities. The N- 1 derived benzotriazole 5e and N-2 de- rived benzotriazole 6a exhibited valuable inhibitory efficacy against some tested strains. Especially, derivative 6a gave superior antifungal efficacies against C. utilis, S. cerevisiae and A. flavus （MIC^0.01, 0.02, 0.02 gmol/mL, respectively） to Fluconazole. The drug combination of compound 5e or 6a with antibacterial Chloromycin, Nor- floxacin and antifungal Fluconazole respectively showed stronger antimicrobial efficiency with less dosage and broader antimicrobial spectrum than their separated use alone. The preliminary interaction with calf thymus DNA revealed that compound 6a could intercalate into DNA to form 6a-DNA supramolecular complex which might be a factor to exert its powerful bioactivity. Molecular docking study indicated strong binding of compound 6a with DNA gyrase. The structural parameters such as molecular orbital energy and molecular electrostatic potential of compound 6a were also investigated, which provided better understanding for its good antimicrobial activity.
