1. Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity.
- Author
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Benoit AR, Schiaffo C, Salomon CE, Goodell JR, Hiasa H, and Ferguson DM
- Subjects
- Aminoacridines chemistry, Anti-Bacterial Agents chemistry, Dose-Response Relationship, Drug, Methicillin pharmacology, Microbial Sensitivity Tests, Molecular Structure, Staphylococcus aureus drug effects, Structure-Activity Relationship, Aminoacridines chemical synthesis, Aminoacridines pharmacology, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology
- 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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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