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

Adam R. Benoit, Charles Schiaffo, Christine E. Salomon, John R. Goodell, Hiroshi Hiasa, David M. Ferguson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3014-3017
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number14
DOIs
StatePublished - Jul 15 2014

Bibliographical note

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • Acridines
  • Amphiphiles
  • Antimicrobials
  • Drug design
  • Intercalation
  • MRSA
  • SAR
  • Synthesis
  • Topoisomerase

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