title: Synthesis and evaluation of N-alkyl-9-aminoacridines with antibacterial activity.
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.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Benoit
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Schiaffo
authors.affiliation: Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Salomon
authors.affiliation: Department of Chemistry, Illinois State University, Normal, IL 61790-4160, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Goodell
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiasa
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, United States; Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: ferguson@umn.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Ferguson
mesh_terms: D000609:Aminoacridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000609:Aminoacridines; D000900:Anti-Bacterial Agents; D008712:Methicillin
keywords: Acridines; Amphiphiles; Antimicrobials; Drug design; Intercalation; MRSA; SAR; Synthesis; Topoisomerase