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Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity
Adam R Benoit1, Charles Schiaffo1, Christine E Salomon2
1Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, United States.
Abstract:
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.
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