Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity

Bioorg Med Chem Lett. 2014 Jul 15;24(14):3014-7. doi: 10.1016/j.bmcl.2014.05.037. Epub 2014 May 22.


A series of 9-alkylaminoacridines were synthesized and evaluated for activity against two strains of methicillin-resistant and one strain of methicillin-sensitive Staphylococcus aureus. Results are presented that show a clear structure activity relationship between the N-alkyl chain length and antibacterial activity with peak MIC99 values of 2-3 μM for alkyl chains ranging from 10 to 14 carbons in length. Although prior work has linked the function of acridine-based compounds to intercalation and topoisomerase inhibition, the present results show that 9-alkylaminoacridines likely function as amphiphilic membrane-active disruptors potentially in a similar manner as quaternary ammonium antimicrobials.

Keywords: Acridines; Amphiphiles; Antimicrobials; Drug design; Intercalation; MRSA; SAR; Synthesis; Topoisomerase.

MeSH terms

  • Aminoacridines / chemical synthesis*
  • Aminoacridines / chemistry
  • Aminoacridines / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Methicillin / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship


  • Aminoacridines
  • Anti-Bacterial Agents
  • Methicillin