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

Chin J Nat Med. 2018 Oct;16(10):774-781. doi: 10.1016/S1875-5364(18)30117-1.


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-π stacked, π-cationic, and π-anionic interactions were responsible for the strong binding of the compounds with the target protein-DNA complex.

Keywords: Antimicrobial drugs; Berberine derivatives; Molecular docking; SAR; Topoisomerase II DNA gyrase.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology*
  • Bacteria / drug effects
  • Berberine / chemical synthesis
  • Berberine / chemistry*
  • Berberine / pharmacology*
  • Drug Design
  • Fungi / drug effects
  • Molecular Docking Simulation
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Antifungal Agents
  • Berberine