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

doi:10.1016/j.bmcl.2014.05.037

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

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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 language	English (US)
Pages (from-to)	3014-3017
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2014.05.037
State	Published - Jul 15 2014

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

Keywords

Acridines
Amphiphiles
Antimicrobials
Drug design
Intercalation
MRSA
SAR
Synthesis
Topoisomerase

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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.",

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AU - Schiaffo, Charles

AU - Salomon, Christine E.

AU - Goodell, John R.

AU - Hiasa, Hiroshi

AU - Ferguson, David M.

PY - 2014/7/15

Y1 - 2014/7/15

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AB - 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.

KW - Acridines

KW - Amphiphiles

KW - Antimicrobials

KW - Drug design

KW - Intercalation

KW - MRSA

KW - SAR

KW - Synthesis

KW - Topoisomerase

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

Abstract

Bibliographical note

Keywords

UN SDGs

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