Antiproliferative and antibacterial potential of tetrahexylammonium bromide‑based ionic liquids

Popescu,Roxana; Filimon,Marioara Nicoleta; Vlad,Daliborca Cristina; Verdes,Doina; Moatar,Aurica; Moise,Georgiana; Guran,Kristine; Caraba,Ion Valeriu; Ciochina,Liliana Petculescu; Pinzaru,Iulia; Dehelean,Cristina Adriana; Dumitrescu,Gabi

doi:10.3892/etm.2021.10104

Antiproliferative and antibacterial potential of tetrahexylammonium bromide‑based ionic liquids

Authors:
- Roxana Popescu
- Marioara Nicoleta Filimon
- Daliborca Cristina Vlad
- Doina Verdes
- Aurica Moatar
- Georgiana Moise
- Kristine Guran
- Ion Valeriu Caraba
- Liliana Petculescu Ciochina
- Iulia Pinzaru
- Cristina Adriana Dehelean
- Gabi Dumitrescu
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Affiliations: Faculty of Medicine, ‘Victor Babes’ University of Medicine and Pharmacy of Timisoara, 300041 Timisoara, Romania, ANAPATMOL Research Center, ‘Victor Babes’ University of Medicine and Pharmacy of Timisoara, 300041 Timisoara, Romania, Faculty of Bioengineering of Animal Resources, ‘Regele Mihai I al României’ Banat University of Agricultural Sciences and Veterinary Medicine, 300645 Timisoara, Romania, Faculty of Pharmacy, ‘Victor Babes’ University of Medicine and Pharmacy of Timisoara, 300041 Timisoara, Romania
Published online on: April 23, 2021 https://doi.org/10.3892/etm.2021.10104
Article Number: 672
Copyright: © Popescu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ionic liquids (ILs) exhibit cytotoxic effects on prokaryotic and eukaryotic cells. In this study, the antibacterial and antiproliferative activities of tetrahexylammonium bromide‑based ILs were investigated. In order to evaluate the therapeutic potential of these ionic liquids, firstly microbiological assay using both Gram‑positive and Gram‑negative bacteria were conducted by employing Disk‑Diffusion and 2,3,5‑triphenyltetrazolium chlorine (TTC) methods to assess the antimicrobial effects. Likewise, the antitumor effects on 2D and 3D cell culture systems were assessed using the human colon cancer Caco‑2 cell line and cytotoxic activity was assessed using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) and Alamar blue assays. Results obtained showed that [CH₃(CH₂)₅]₄N(Br) possesses an antibacterial potential, particularly in the case of two bacteria, S. aureus (Gram₊) and H. influenzae (Gram^‑). Preliminary screening of antiproliferative activity showed moderate activity, except for the concentration of 10 mM. Furthermore, regarding the effect of [CH₃(CH₂)₅]₄N(Br) on tumor cell aggregation, positive outcomes were noted. [CH₃(CH₂)₅]₄N(Br) presents promising and under‑explored potential to improve antibacterial or anticancer therapies.

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1	Busetti A, Crawford DE, Earle MJ, Gilea MA, Gilmore BF, Gorman SP, Laverty G, Lowry AF, McLaughlin M and Seddon KR: Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids. Green Chem. 12:420–425. 2010.
2	Myles L, Gore R, Špulák M, Gathergood N and Connon SJ: Highly recyclable, imidazolium derived ionic liquids of low antimicrobial and antifungal toxicity: A new strategy for acid catalysis. Green Chem. 12:1157–1162. 2010.
3	Endres F: Ionic liquids: Solvents for the electrodeposition of metals and semiconductors. Chemphyschem. 3:144–154. 2002.PubMed/NCBI View Article : Google Scholar
4	Moniruzzaman M, Nakashima K, Kamiya N and Goto M: Recent advances of enzymatic reactions in ionic liquids. Biochem Eng J. 48:295–314. 2010.
5	Ferlin N, Courty M, Gatard S, Spulak M, Quilty B, Beadham I, Ghavre M, Haiss A, Kümmerer K, Gathergood N and Bouquillon S: Biomass derived ionic liquids: Synthesis from natural organic acids, characterization, toxicity, biodegradation and use as solvents for catalytic hydrogenation processes. Tetrahedron. 69:6150–6161. 2013.
6	Messali M: A green microwave-assisted synthesis, characterization and comparative study of new pyridazinium-based ionic liquids derivatives towards corrosion of mild steel in acidic environment. J Mater Environ Sci. 2:174–185. 2011.
7	Messali M, Bousskri A, Anejjar A, Salghi R and Hammouti B: Electrochemical studies of new pyridazinium-based ionic liquid, (1-4-nitro phenyl-1-ethanone) pyridazinium bromide, on carbon steel corrosion in hydrochloric acid medium. Int J Electrochem Sci. 10:4532–4551. 2015.
8	Biswas A, Shogren RL, Stevenson DG, Willett JL and Bhowmik PK: Ionic liquids as solvents for biopolymers: Acylation of starch and zein protein. Carbohydr Polym. 66:546–550. 2006.
9	Talavera-Prieto NM, Ferreira AG, Simões PN, Carvalho PJ, Mattedi S and Coutinho JA: Thermophysical characterization of N-methyl-2-hydroxyethylammoniumcarboxilate ionic liquids. J Chem Thermodyn. 68:221–234. 2014.
10	Petkovic M, Ferguson J, Bohn A, Trindade J, Martins I, Carvalho MB, Leitão MC, Rodrigues C, Garcia H, Ferreira R, et al: Exploring fungal activity in the presence of ionic liquids. Green Chem. 11:889–894. 2009.
11	Iwai N, Nakayama K, Oku J and Kitazume T: Synthesis and antibacterial activity of alaremycin derivatives for the porphobilinogen synthase. Bioorg Med Chem Lett. 21:2812–2815. 2011.PubMed/NCBI View Article : Google Scholar
12	Alberto EE, Rossato LL, Alves SH, Alves D and Braga AL: Imidazolium ionic liquids containing selenium: Synthesis and antimicrobial activity. Org Biomol Chem. 9:1001–1003. 2011.PubMed/NCBI View Article : Google Scholar
13	Coleman D, Špulák M, Garcia MT and Gathergood N: Antimicrobial toxicity studies of ionic liquids leading to a ‘hit’ MRSA selective antibacterial imidazolium salt. Green Chem. 14:1350–1356. 2012.
14	Tavares AP, Rodriguez O, Raquel Cristóvão and Macedo EA: Applications and perspectives ionic liquids: Alterna-tive reactive media for oxidative enzymes. In: Ionic Liquids, Kokorin A (ed). Rijeka, InTech, pp449-516, 2011.
15	Rodríguez O, Cristovao RO, Tavares APM and Macedo EA: Study of the alkyl chain length on laccase stability and enzymatic kinetic with imidazolium ionic liquids. Biotechnol Appl Bioc. 164:524–533. 2011.PubMed/NCBI View Article : Google Scholar
16	Cieniecka-Roslonkiewicz A, Pernak J, Kubis-Feder J, Ramani A, Robertson AJ and Seddo KR: Synthesis, anti-microbial activities and anti-electrostatic properties of phosphonium-based ionic liquids. Green Chem. 7:855–862. 2005.
17	Carson L, Chau PK, Earle MJ, Gilea MA, Gilmore BF, Gorman SP, McCann MT and Seddon KR: Antibiofilm activities of 1-alkyl-3-methylimidazolium chloride ionic liquids. Green Chem. 11:492–497. 2009.
18	Messali M: Eco-friendly synthesis of a new class of pyridinium-based ionic liquids with attractive antimicrobial activity. Molecules. 20:14936–14949. 2015.PubMed/NCBI View Article : Google Scholar
19	Egorova KS, Gordeev EG and Ananikov VP: Biological activity of ionic liquids and their application in pharmaceutics and medicine. Chem Rev. 117:7132–7189. 2017.PubMed/NCBI View Article : Google Scholar
20	Kapałczyńska M, Kolenda T, Przybyła W, Zajączkowska M, Teresiak A, Filas V, Ibbs M, Bliźniak R, Łuczewski L and Lamperska K: 2D and 3D cell cultures-a comparison of different types of cancer cell cultures. Arch Med Sci. 14:910–919. 2018.PubMed/NCBI View Article : Google Scholar
21	CLSI. Performance standards for antimicrobial susceptibility testing. 27th edition. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute, 2017.
22	Kurnia KA, Sintra TE, Neves CM, Shimizu K, Canongia Lopes JN, Goncalves F, Ventura SP, Freire MG, Santos LM and Coutinho JA: The effect of the cation alkyl chain branching on mutual solubilities with water and toxicities. Phys Chem Chem Phys. 16:19952–19963. 2014.PubMed/NCBI View Article : Google Scholar
23	Ohno H, Fujita K and Kohno Y: Is seven the minimum number of water molecules per ion pair for assured biological activity in ionic liquid-water mixtures? Phys Chem Chem Phys. 17:14454–14460. 2015.PubMed/NCBI View Article : Google Scholar
24	Wang Y, Li H and Han SA: A theoretical investigation of the interactions between water molecules and ionic liquids. J Phys Chem B. 110:24646–24651. 2006.PubMed/NCBI View Article : Google Scholar
25	Zheng Z, Xu Q, Guo J, Qin J, Mao H, Wang B and Yan F: Structure-antibacterial activity relationships of imidazolium-type ionic liquid monomers, poly(ionic liquids) and poly(ionic liquid) membranes: Effect of alkyl chain length and cations. ACS Appl Mater Interfaces. 8:12684–12692. 2016.PubMed/NCBI View Article : Google Scholar
26	Khudyakov JI, D'Haeseleer P, Borglin SE, Deangelis KM, Woo H, Lindquist EA, Hazen TC, Simmons BA and Thelen MP: Global transcriptome response to ionic liquid by a tropical rain forest soil bacterium, Enterobacter lignolyticus. Proc Natl Acad Sci USA. 109:E2173–E2182. 2012.PubMed/NCBI View Article : Google Scholar
27	Borkowski A, Kowalczyk P, Czerwonka G, Cieśla J, Cłapa T, Misiewicz A, Szala M and Drabik M: Interaction of quaternary ammonium ionic liquids with bacterial membranes-studies with Escherichia coli r1-r4-type lipopolysaccharides. J Mol Liquids. 246:282–289. 2017.
28	Kowalczyk P, Borkowski A, Czerwonka G, Cłapa T, Cieśla J, Misiewicz A, Borowiec M and Szala M: The microbial toxicity of quaternary ammonium ionic liquids is dependent on the type of lipopolysaccharide. J Mol Liquids. 266:540–547. 2018.
29	Dauborca VC, Dumitrascu V, Popescu R, Cimporescu A, Vlad CS, Flangea C, Grecu DS, Vágvölgyi C, Papp T and Horhat FG: Gas chromatography-mass spectrometry evidences for new chemical insights of momordica charantia. Rev Chim. 66:1914–1920. 2015.
30	Moatar AE, Vlad CS, Vlad DC, Verdes DM, Filimon MN, Bloju O, Borcan F, Dehelean CA and Dumitrascu V: Evaluation of antiproliferative potential of Myrmecodia pendans and its activity on il-8 secretion in colon cancer cell. Farmacia. 68:710–714. 2020.
31	O'Toole GA, Wathier M, Zegans ME, Shanks RM, Kowalski R and Grinstaff MW: Diphosphonium ionic liquids as broad-spectrum antimicrobial agents. Cornea. 31:810–816. 2012.PubMed/NCBI View Article : Google Scholar
32	Hou XD, Liu QP, Smith TJ, Li N and Zong MH: Evaluation of toxicity and biodegradability of cholinium amino acids ionic liquids. PLoS One. 8(e59145)2013.PubMed/NCBI View Article : Google Scholar
33	Docherty KM, Joyce MV, Kulacki KJ and Kulpa CF: Microbial biodegradation and metabolite toxicity of three pyridinium-based cation ionic liquids. Green Chem. 12:701–712. 2010.
34	Hough-Troutman WL, Smiglak M, Griffin S, Matthew Reichert W, Mirska I, Jodynis-Liebert J, Adamska T, Nawrot J, Stasiewicz M, Rogers RD and Pernak J: Ionic liquids with dual biological function: Sweet and anti-microbial, hydrophobic quaternary ammonium-based salts. New J Chem. 33:26–33. 2009.
35	Stoimenovski J, MacFarlane DR, Bica K and Rogers RD: Crystalline vs. ionic liquid salt forms of active pharmaceutical ingredients: A position paper. Pharm Res. 27:521–526. 2010.PubMed/NCBI View Article : Google Scholar
36	Tran CD, Prosenc F and Franko M: Facile synthesis, structure, biocompatibility and antimicrobial property of gold nanoparticle composites from cellulose and keratin. J Colloid Interface Sci. 510:237–245. 2018.PubMed/NCBI View Article : Google Scholar
37	Gilmore BF: Antimicrobial ionic liquids, In: Ionic Liquids: Applications and Perspectives, Kokorin A (ed). InTech, Rijeka, pp587-604, 2011.
38	Yu Y and Nie Y: Toxicity and antimicrobial activities of ionic liquids with halogen anion. J Environ Prot. 2:298–303. 2011.
39	Ventura SPM, Gurbisz M, Ghavre M, Ferreira FMM, Gonçalves F, Beadham I, Quilty B, Coutinho JAP and Gathergood N: Imidazolium and pyridinium ionic liquids from mandelic acid derivatives: Synthesis and bacteria and algae toxicity evaluation. ACS Sustain Chem Eng. 1:393–402. 2013.
40	Payagala T and Armstrong DW: Chiral ionic liquids: A compendium of syntheses and applications (2005-2012). Chirality. 24:17–53. 2012.PubMed/NCBI View Article : Google Scholar
41	Haragus H, Vermesan D, Lazureanu V, Ferdean N, Radu D, Prejbeanu R and Niculescu M: Antibiotic loaded cement spacers for two stage treatment of periprosthetic joint infections. Rev Chim (Bucharest). 67:764–767. 2016.
42	Messali M, Aouad MR, El-Sayed WS, Ali AA, Ben Hadda T and Hammouti B: New eco-friendly 1-alkyl-3-(4-phenoxybutyl) imidazolium-based ionic liquids derivatives: A green ultrasound-assisted synthesis, characterization, antimicrobial activity and POM analyses. Molecules. 19:11741–11759. 2014.PubMed/NCBI View Article : Google Scholar
43	Miskiewicz A, Ceranowicz P, Szymczak M, Bartuś K and Kowalczyk P: The use of liquids ionic fluids as pharmaceutically active substances helpful in combating nosocomial infections induced by Klebsiella pneumoniae New Delhi strain, Acinetobacter baumannii and Enterococcus species. Int J Mol Sci. 19(2779)2018.PubMed/NCBI View Article : Google Scholar
44	Egorova KS, Seitkalieva MM, Posvyatenko AV and Ananikov VP: An unexpected increase of toxicity of amino acid-containing ionic liquids. Toxicol Res. 4:152–159. 2015.
45	Frade RFM, Matias A, Branco LC, Afonsoc CAM and Duarte CMM: Effect of ionic liquids on human colon carcinoma HT-29 and CaCo-2 cell lines. Green Chem. 9:873–877. 2007.
46	Frade RFM, Rosatella AA, Marques CS, Branco LC, Kulkarni PS, Mateus NMM, Afonso CAM and Duarte CMM: Toxicological evaluation on human colon carcinoma cell line (CaCo-2) of ionic liquids based on imidazolium, guanidinium, ammonium, phosphonium, pyridinium and pyrrolidinium cations. Green Chem. 11:1660–1665. 2009.
47	García-Lorenzo A, Tojo E, Tojo J, Teijeira M, Rodríguez-Berrocal FJ, Pérez González M and Martínez-Zorzano VS: Cytotoxicity of selected imidazolium-derived ionic liquids in the human Caco-2 cell line. Sub-structural toxicological interpretation through a QSAR study. Green Chem. 10:508–516. 2008.
48	Kumar V and Malhotra SV: Study on the potential anti-cancer activity of phosphonium and ammonium-based ionic liquids. Bioorg Med Chem Lett. 19:4643–4646. 2009.PubMed/NCBI View Article : Google Scholar
49	Li X, Ma J and Wang J: Cytotoxicity, oxidative stress, and apoptosis in HepG2 cells induced by ionic liquid 1-methyl-3-octylimidazolium bromide. Ecotoxicol Environ Saf. 120:342–348. 2015.PubMed/NCBI View Article : Google Scholar
50	Ranke J, Mölter K, Stock F, Bottin-Weber U, Poczobutt J, Hoffmann J, Ondruschka B, Filser J and Jastorff B: Biological effects of imidazolium ionic liquids with varying chain lengths in acute vibrio fischeri and WST-1 cell viability assays. Ecotoxicol Environ Saf. 58:396–404. 2004.PubMed/NCBI View Article : Google Scholar
51	Flieger J and Flieger M: Ionic liquids toxicity-benefits and threats. Int J Mol Sci. 21(6267)2020.PubMed/NCBI View Article : Google Scholar
52	Zakrewsky M, Lovejoy KS, Kern TL, Miller TE, Le V, Nagy A, Goumas AM, Iyer RS, Del Sesto RE, Koppisch AT, et al: Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proc Natl Acad Sci USA. 111:13313–13318. 2014.PubMed/NCBI View Article : Google Scholar
53	Miwa Y, Hamamoto H, Hikake S and Kuwabara Y: A phase I, randomized, open-label, cross-over study of the pharmacokinetics, dermal tolerability, and safety of MRX-7EAT etodolac-lidocaine topical patch in healthy volunteers. J Pain. 14 (Suppl 4)(S72)2013.