Synthesis and biological evaluation of novel cyanuric acid-tethered tris-pyridinium derivatives

Vereshchagin, Anatoly N.; Frolov, Nikita A.; Minaeva, Alexandra P.; Detusheva, Elena V.; Derkach, Yana V.; Egorov, Mikhail P.

doi:10.1016/j.mencom.2021.04.028

Cited by 7 publications

(18 citation statements)

References 16 publications

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“…The highest level of resistance was noted for A. baumannii and P. aeruginosa . This can be justified by specific features of these bacterial strains and it is consistent with the results of our previous studies [ 19 ]. It should be noted that Gram-positive S. aureus were more sensitive to the studied QACs than Gram-negative bacteria.…”

Section: Resultssupporting

confidence: 92%

Microbiological Evaluation of Novel Bis-Quaternary Ammonium Compounds: Clinical Strains, Biofilms, and Resistance Study

et al. 2022

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This work is devoted to the investigation of biocidal properties of quaternary ammonium compounds (QACs) based on pyridine structures with aromatic spacers, and their widely known analogs, against clinically significant microorganisms. This study is focused on investigating their antimicrobial activity (minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs)), antibiofilm properties (minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs)), synergetic effect with different alcohols in antiseptic formulations, and bacterial resistance development. It was shown that all combined analogue preparations had a higher level of antibacterial activity against the tested bacterial strains, with a 16- to 32-fold reduction in MICs and MBCs compared to previously used antiseptic preparations. Moreover, hit-QACs demonstrated a stable effect against Gram-negative E. coli, K. pneumoniae, and A. baumannii within a month of incubation. Overall results indicated a high level of antibacterial activity of pyridine-based QACs.

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Section: Resultssupporting

confidence: 92%

Microbiological Evaluation of Novel Bis-Quaternary Ammonium Compounds: Clinical Strains, Biofilms, and Resistance Study

et al. 2022

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“…Fortunately, many research groups have been developing alternative approaches to the synthesis of disinfectant amphiphiles over these same recent decades. This has resulted in a growing variety of compound architectures, including the number of cationic ammonium centers, [15][16][17][18] variation in nonpolar groups, [19][20][21] and even more recently a push towards nonnitrogenous amphiphilic disinfectant structures. [22,23] The inclusion of more than one cationic center has repeatedly been shown to engender superior antimicrobial activity, as well as diminished susceptibility to bacterial resistance.…”

Section: Introductionmentioning

confidence: 99%

Double BAC and Triple BAC: A Systematic Analysis of the Disinfectant Properties of Multicationic Derivatives of Benzalkonium Chloride (BAC)

Toles

Sanchez

et al. 2023

ChemMedChem

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Over the past decades, the shortcomings of established quaternary ammonium disinfectants have become increasingly clear. Although benzalkonium chloride (BAC) has enjoyed nearly a century of significantly protecting human health through surgical preparation, home use, and industrial applications, increasing levels of bacterial resistance have rendered it decreasingly effective. In light of more recent efforts that have informed us that multicationic amphiphilic disinfectants show both higher activity as well as diminished susceptibility to resistance, we embarked on the preparation of 27 multicationic QACs in an attempt to clearly document structure‐activity relationships of next‐generation BAC structures. Select biscationic BAC derivatives demonstrate single‐digit micromolar activity against all seven bacteria tested and MIC values of 2‐ to 32‐fold better than BAC. Particularly notable is the improvement against the more concerning bacteria like Acinetobacter baumannii and Pseudomonas aeruginosa, which pose a modern threat to legacy disinfectants like BAC. With simple synthetic paths, consistently high yields (averaging ∼80 %), and strong biological activity, potent structures with clear SAR trends and strong therapeutic indices have been established.

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“…41 It is also a simple and affordable way to obtain multicationic compounds based on isocyanuric acid. 42 However, the limited number of available structural motifs is still a critical limiting factor.…”

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confidence: 99%

“…47 Compounds with a short (C2) alkyl chain in the linker have previously been shown to exhibit moderate activity against laboratory pathogen strains. 42 Here, we extended the study by determining their efficacy against multiresistant strains. The data are summarized in Table 2.…”

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confidence: 99%

“…Previously, a series of trispyridinium salts based on 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazinan-2,4,6trione was prepared by our group. 42 They demonstrated modest activity against ESKAPE pathogens but were inferior in effectiveness to octenidine dihydrochloride (OCT) and, in some cases, cetylpyridinium chloride (CPC). In addition, the proposed synthesis procedure severely limited the possibility of varying the linker structure, preventing an increase in the activity.…”

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confidence: 99%

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Multicationic Quaternary Ammonium Compounds: A Framework for Combating Bacterial Resistance

et al. 2023

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During previous stages of research, high biocidal activity toward microorganism archival strains has been used as the main indicator in the development of new antiseptic formulations. Although this factor remains one of the most important characteristics of biocide efficiency, the scale of antimicrobial resistance spread causes serious concern. Therefore, focus shifts toward the development of formulations with a stable effect even in the case of prolonged contact with pathogens. Here, we introduce an original isocyanuric acid alkylation method with the use of available alkyl dichlorides, which opened access to a wide panel of multi-QACs with alkyl chains of various lengths between the nitrogen atoms of triazine and pyridine cycles. We used a complex approach for the resulting series of 17 compounds, including their antibiofilm properties, bacterial tolerance development, and antimicrobial activity toward multiresistant pathogenic strains. As a result of these efforts, available compounds have shown higher levels of antibacterial activity against ESKAPE pathogens than widely used commercial QACs. Hit compounds possessed high activity toward clinical bacterial strains and have also demonstrated a long-term biocidal effect without significant development of microorganism tolerance. The overall results indicated a high level of antibacterial activity and the broad application prospects of multi-QACs based on isocyanuric acid against multiresistant bacterial strains.

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Synthesis and biological evaluation of novel cyanuric acid-tethered tris-pyridinium derivatives

Cited by 7 publications

References 16 publications

Microbiological Evaluation of Novel Bis-Quaternary Ammonium Compounds: Clinical Strains, Biofilms, and Resistance Study

Microbiological Evaluation of Novel Bis-Quaternary Ammonium Compounds: Clinical Strains, Biofilms, and Resistance Study

Double BAC and Triple BAC: A Systematic Analysis of the Disinfectant Properties of Multicationic Derivatives of Benzalkonium Chloride (BAC)

Multicationic Quaternary Ammonium Compounds: A Framework for Combating Bacterial Resistance

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