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

Research output: Contribution to journal › Article › peer-review

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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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2014.05.037

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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.",

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AU - Benoit, Adam R.

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

N2 - 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.

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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