Novel berberine derivatives:Design,synthesis,antimicrobial effects,and molecular docking studies

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.