From antimicrobial activity to mechanism of resistance: the multifaceted role of simple quaternary ammonium compounds in bacterial eradication

Minbiole, Kevin P. C.; Jennings, Megan C.; Ator, Laura E.; Black, Jacob W.; Grenier, Melissa C.; LaDow, Jade E.; Caran, Kevin L.; Seifert, Kyle; Wuest, William M.

doi:10.1016/j.tet.2016.01.014

Cited by 94 publications

(74 citation statements)

References 30 publications

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“…[6] Recent efforts have been made in the development of QACs bearing multiple cationic moieties, which confer improved ability to both destroy bacteria and eradicate biofilms. [7] …”

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confidence: 99%

An Investigation into Rigidity–Activity Relationships in BisQAC Amphiphilic Antiseptics

et al. 2018

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Twenty-one mono- and biscationic quaternary ammonium amphiphiles (monoQACs and bisQACs) were rapidly prepared in order to investigate the effects of rigidity of a diamine core structure on antiseptic activity. As anticipated, bioactivity against a panel of 6 bacteria including MRSA strains was strong for bisQAC structures, and clearly correlated to the length of non-polar side chains. Modest advantages were noted for amide-containing side chains, as compared to straight-chained alkyl substituents. Surprisingly, antiseptics with more rigidly disposed side chains, such as those in DABCO-12,12, showed the highest level of antimicrobial activity, with single-digit MIC values or better against the entire bacterial panel, including submicromolar activity against a MRSA strain.

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“…[6] Recent efforts have been made in the development of QACs bearing multiple cationic moieties, which confer improved ability to both destroy bacteria and eradicate biofilms. [7] …”

mentioning

confidence: 99%

An Investigation into Rigidity–Activity Relationships in BisQAC Amphiphilic Antiseptics

et al. 2018

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“…Broad-spectrum antimicrobial activity [40,41] has made many QACs such as benzalkonium chloride, miramistin, and cetylpyridinium chloride, the useful hygienic adjuncts in disinfectant formulations, and they have also been used in therapy of patients with local pyoinflammatory processes. QACs can also be active against the main pathogenic fungi, such as Candida albicans [42], Cryptococcus neoformans [43], Saccharomyces cerevisiae [44], and Aspergillus flavus [45].…”

Section: Antimycotic Activitymentioning

confidence: 99%

Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

Garipov

Pavelyev

Lisovskaya

et al. 2017

Journal of Chemistry

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Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterial in vitro activity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine) and antibacterial/antiseptic (miramistin, benzalkonium chloride) agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci and Escherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilmembedded forms.

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“…The highly centralized cationic center of Gemini‐QA salts could form potent attractive interactions with the predominantly anionic biological surface, leading to membrane disruption and ultimate bacteria lysis . For instance, multi‐cationic QA salts was capable of strongly damaging bacterial biofilms on polymer surface as well as tending to escape resistance mechanisms of mono‐cationic QA structures . Enlightened by these reports, we proposed the hypothesis that introduction of N ‐chloramine units to a Gemini‐QA structure may afford novel “composite” N ‐chloramines with highly efficacious biocidal activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Gemini‐QA N‐Chloramine Biocides for Antibacterial Applications

Wang

Jia

et al. 2019

ChemistrySelect

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Gemini‐quaternary ammonium (QA) N‐chloramines were synthesized by covalently bonding two N‐chloramine units via a Gemini‐QA core with varied alkyl linkers. Preliminary antibacterial tests showed that Gemini‐QA N‐chloramine exerted superior biocidal efficacy in contrast to previous developed QA N‐chloramine counterpart probably by means of “team effort” contact killings. Futhermore, the analog with linker of ‐(CH2)10‐ exhibited the highest antibacterial efficacy probably caused by its favorable membrane penetration. This work may provide vital references to develop multi‐cationic N‐chloramines with even higher biocidal activity, which may be indispensable for combateing with bacteria resiatance.

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From antimicrobial activity to mechanism of resistance: the multifaceted role of simple quaternary ammonium compounds in bacterial eradication

Abstract: Supplementary material containing full biological data and procedures, and compound preparation and characterization for all new compounds, may be found online at ________.

Cited by 94 publications

References 30 publications

An Investigation into Rigidity–Activity Relationships in BisQAC Amphiphilic Antiseptics

An Investigation into Rigidity–Activity Relationships in BisQAC Amphiphilic Antiseptics

Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

Synthesis of Gemini‐QA N‐Chloramine Biocides for Antibacterial Applications

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