Antimicrobial and Toxicity Evaluation of Imidazolium-Based Dicationic Ionic Liquids with Dicarboxylate Anions.

Bruna L Kuhn,Gustavo P Silveira,Edilma E Da Silva,Nilo Zanatta,Taís F A Kaminski,Bianca M B C Johann,Ânderson R Carvalho,FéLix A A Soares,Clarissa P Frizzo,TáSsia L Da Silveira,Alexandre M Fuentefria

doi:10.3390/pharmaceutics13050639

Bruna L Kuhn, Gustavo P Silveira + Show 9 more

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https://doi.org/10.3390/pharmaceutics13050639

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Abstract

Imidazolium-based dicationic ILs (DILs) presenting antimicrobial activity and relatively low toxicity are highly desirable and are envisioned for use in live tissue to prevent bacterial or fungal infections. In this context, we present here DILs with dicarboxylate anions [Cn(MIM)2[Cn(MIM)2][CO2-(CH2)mCO2], in which n = 4, 6, 8, and 10, and m = 0, 1, 2, 3, 4, and 5. The results showed that DILs with an alkyl chain spacer of ten carbons were active against yeasts and the bacterial strains tested. However, most of the DILs were cytotoxic and toxic at 1 mM. By contrast, DILs with alkyl chains possessing less than ten carbons were active against some specific Candidas and bacteria (mainly S. aureus), and they showed moderate cytotoxicity. The best activity against Gram-positive bacteria was observed for [C4(MIM)2][Pim] toward MRSA. For the DILs described herein, their level of toxicity against C. elegans was lower than that of most of the mono- and dicationic IL analogs with other anions. Our results showed that the presence of carboxylate anions reduces the toxicity of DILs compared to DILs containing halide anions, which is particularly significant to the means of designing biologically active compounds in antimicrobial formulations.

Highlights

Given the possible applications in drug synthesis, drug delivery systems, and biomedical materials, the antimicrobial, cytotoxic, and toxic properties of ionic liquids (ILs) have attracted significant attention from medical scientists
The results showed that, after 24 h, all dicationic ILs (DILs) were active in concentrations below 1 mM
Considering these results for monocationic ILs and the ones presented for DILs, the influence of the anion decreases as the alkyl chain lengthens, which suggests that the cationic moiety has a dominant effect on the toxicity of monocationic ILs

Summary

Introduction

Given the possible applications in drug synthesis, drug delivery systems, and biomedical materials, the antimicrobial, cytotoxic, and toxic properties of ionic liquids (ILs) have attracted significant attention from medical scientists. A diversity of measures of antimicrobial activity has been reported for all classes of ILs to evaluate the antimicrobial response of a widespread range of microorganisms [1,2]. The mechanisms of antimicrobial activity in ILs have not yet been fully elucidated; it has been largely described that the alkyl chains are the protagonist, most likely by disturbing the chemical structure of the biological membranes [2,3,4]. The highest antimicrobial activity was observed in ILs with an alkyl chain length of 12 or 14 carbons. A marked reduction in antimicrobial activity for IL with alkyl chains with more than 16 or less than 10 carbons was reported [2,3,4].

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