SpringerLink
Log in

Imidazolium-based ionic liquids disrupt saccharomyces cerevisiae cell membrane integrity

  • Original Paper
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

Ionic liquids (ILs) are interesting chemical compounds that have a wide range of industrial and scientific applications. They have extraordinary properties, such as the tunability of many of their physical properties and, accordingly, their activities; and the ease of synthesis methods. Hence, they became important building blocks in catalysis, extraction, electrochemistry, analytics, biotechnology, etc. This study determined antifungal activities of various imidazolium-based ionic liquids against yeast Saccharomyces cerevisiae via minimum inhibitory concentration (MIC) estimation method. Increasing the length of the alkyl group attached to the imidazolium cation, enhanced the antifungal activity of the ILs, as well as their ability of the disruption of the cell membrane integrity. FTIR studies performed on the S. cerevisiae cells treated with the ILs revealed alterations in the biochemical composition of these cells. Interestingly, the alterations in fatty acid content occurred in parallel with the increase in the activity of the molecules upon the increase in the length of the attached alkyl group. This trend was confirmed by statistical analysis and machine learning methodology. The classification of antifungal activities based on FTIR spectra of S. cerevisiae cells yielded a prediction accuracy of 83%, indicating the pharmacy and medicine industries could benefit from machine learning methodology. Furthermore, synthesized ionic compounds exhibit significant potential for pharmaceutical and medical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  • Alreqeb S, Ergüden B (2024) Chalcone derivatives disrupt cell membrane integrity of Saccharomyces cerevisiae cells and alter their biochemical composition. Arch Microbiol 206(1):34

    Article  CAS  Google Scholar 

  • Andrade JT, Santos FRS, Lima WG, Sousa CDF, Oliveira LSFM, Ribeiro RIMA, Gomes AJPS, Araújo MGF, Villar JAFP, Ferreira JMS (2018) Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents. J of Antibiotics 71:702–712

    Article  CAS  Google Scholar 

  • Avirdi E, Paumo HK, Kamdem BP, Singh MB, Kumari K, Katata-Seru L, Bahadur I (2023) Imidazolium-based ionic liquid-assisted silver nanoparticles and their antibacterial activity: experimental and density functional theory studies. ACS Omega 8(45):42976–42986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker MJ, Trevisan J, Bassan P, Bhargava R, Butler HJ, Dorling KM, Martin FL (2014) Using fourier transform IR spectroscopy to analyze biological materials. Nat Protoc 9(8):1771–1791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergamo VZ, Donato RK, Dalla Lana DF, Donato KJZ, Ortega GG, Schrekker HS, Fuentefria AM (2015) Imidazolium salts as antifungal agents: strong antibiofilm activity against multidrug-resistant Candida tropicalis isolates. Let Appl Microbiol 60(1):66–71

    Article  CAS  Google Scholar 

  • Borowiecki P, Milner-Krawczyk M, Brzezin′ska D, Wielechowska M, Plenkiewicz J (2013) Synthesis and antimicrobial activity of imidazolium and triazolium chiral ionic liquids. Eur J Org Chem 2013:712–720

    Article  CAS  Google Scholar 

  • Çelik F, Ünver Y, Aydın A, Güler Hİ, Bektaş Kİ (2024) Synthesis, characterization and biological activity of novel ionic liquids with bis-imidazole moieties: antitumor, antimicrobial effects and molecular docking studies. Org Commun 17(1):23–37

    Google Scholar 

  • Charan KP, Ranjan P, Manojkumar K, Pothanagandhi N, Jha PC, Khedkar VM, Sivaramakrishna A, Vijayakrishna K (2015) Evaluation of imidazolium-based ionic liquids towards vermicidal activity: in vitro and in silico studies. RSC Adv 5(92):75415–75424

    Article  CAS  Google Scholar 

  • Cheng Y, Du Z, Zhu H, Guo X, He X (2016) Protective effects of arginine on Saccharomyces cerevisiae against ethanol stress. Sci Rep 6(1):31311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornellas A, Perez L, Comelles F, Ribosa I, Manresa A (2011) Self-aggregation and antimicrobial activity of imidazolium and pyridinium based ionic liquids in water solutions. J Colloid Interface Sci 355:164–171

    Article  CAS  PubMed  Google Scholar 

  • Corte L, Rellini P, Roscini L, Fatichenti F, Cardinali G (2010) Development of a novel, FTIR (fourier transform infrared spectroscopy) based, yeast bioassay for toxicity testing and stress response study. Anal Chim Acta 659(1–2):258–265

    Article  CAS  PubMed  Google Scholar 

  • da Cunha RB, Fonseca LP, Calado CR (2021) Simultaneous elucidation of antibiotic mechanism of action and potency with high-throughput fourier-transform infrared (FTIR) spectroscopy and machine learning. Appl Microbiol Biotech 105:1269–1286

    Article  Google Scholar 

  • Dalla Lana DF, Donato RK, Bündchen C, Guez CM, Bergamo VZ, de Oliveira LFS, Machado MM, Schrekker HS, Fuentefria AM (2015) Imidazolium salts with antifungal potential against multidrug-resistant dermatophytes. J Appl Microbiol 119(2):377–388

    Article  CAS  PubMed  Google Scholar 

  • Egorova KS, Gordeev EG, Ananikov VP (2017) Biological activity of ionic liquids and their application in pharmaceutics and medicine. Chem Rev 117(10):7132–7189

    Article  CAS  PubMed  Google Scholar 

  • Ergüden B, Lüleci HB, Ünver Y (2023) Chalcone Schiff bases disrupt cell membrane integrity of Saccharomyces cerevisiae and Candida albicans cells. Arch Microbiol 205(6):246

    Article  PubMed  Google Scholar 

  • Fojtášková J, Koutník I, Vráblová M, Sezimová H, Maxa M, Obalová L, Pánek P (2020) Antibacterial, antifungal and ecotoxic effects of ammonium and imidazolium ionic liquids synthesized in microwaves. Molecules 25(21):5181

    Article  PubMed  PubMed Central  Google Scholar 

  • Garcia-Gonzalez L, Geeraerd AH, Mast J, Briers Y, Elst K, Van Ginneken L, Van Impe JF, Devlieghere F (2010) Membrane permeabilization and cellular death of Escherichia coli, Listeria monocytogenes and Saccharomyces cerevisiae as induced by high pressure carbon dioxide treatment. Food Microbiol 27(4):541–549

    Article  CAS  PubMed  Google Scholar 

  • Gilmore BF, Earle MJ (2011) Development of ionic liquid biocides against microbial biofilm. Chim Oggi 29:50–53

    CAS  Google Scholar 

  • Gravel J, Schmitzer AR (2017) Imidazolium and benzimidazolium-containing compounds: from simple toxic salts to highly bioactive drugs. Org Biomol Chem 15(5):1051–1071

    Article  CAS  PubMed  Google Scholar 

  • Hossain CM, Ryan LK, Gera M, Choudhuri S, Lyle N, Ali KA, Diamond G (2022) Antifungals and drug resistance. Encyclopedia 2(4):1722–1737

    Article  Google Scholar 

  • Hryniewicka A, Niemirowicz-Laskowska K, Wielgat P, Car H, Hauschild T, Morzycki JW (2021) Dehydroepiandrosterone derived imidazolium salts and their antimicrobial efficacy. Bioorg Chem 108:104550

    Article  CAS  PubMed  Google Scholar 

  • Iwai N, Nakauama K, Kitazume T (2011) Antibacterial activities of imidazolium, pyrrolidinium and piperidinium salts. Bioorg Med Chem Lett 21:1728–1729

    Article  CAS  PubMed  Google Scholar 

  • Jung Y (2018) Multiple predicting K-fold cross-validation for model selection. J Nonparametric Stat 30(1):197–215

    Article  Google Scholar 

  • Kobayashi F, Odake S (2017) Intracellular acidification and damage of cellular membrane of Saccharomyces pastorianus by low-pressure carbon dioxide microbubbles. Food Control 71:365–370

    Article  CAS  Google Scholar 

  • Konuk H, Ergüden B (2020) Phenolic –OH group is crucial for the antifungal activity of terpenoids via disruption of cell membrane integrity. Folia Microbiol 65(4):775–783

    Article  CAS  Google Scholar 

  • Kumar Y, Wani FA, Ahmedi S, Shamsi A, Nadeem M, Manzoor N, Kamli MR, Malik MA, Rizvi MA, Patel R (2024) In vitro antifungal activity, cytotoxicity and binding analysis of imidazolium based ionic liquids with fluconazole: DFT and spectroscopic study. J Mol Liq 401:124631

    Article  CAS  Google Scholar 

  • Lockhart SR, Chowdhary A, Gold JAW (2023) The rapid emergence of antifungal-resistant human-pathogenic fungi. Nat Rev Microbiol 21:818–832

    Article  CAS  PubMed  Google Scholar 

  • Luczak J, Jungnickel C, Laska I, Stolte S, Hupka J (2010) Antimicrobial and surface activity of 1-alkyl-3-methyl imidazolium derivatives. Green Chem 12:593–601

    Article  CAS  Google Scholar 

  • Mahapatra DK, Bharti SK, Asati V (2015) Chalcone scaffolds as anti-infective agents: Structural and molecular target perspectives. Eur J Med Chem 101:496–524

    Article  CAS  PubMed  Google Scholar 

  • Messali M, Aouad MR, Ali AA, Rezki N, Ben Hadda T, Hammouti B (2015) Synthesis, characterization, and POM analysis of novel bioactive imidazolium-based ionic liquids. Med Chem Res 24:1387–1395

    Article  CAS  Google Scholar 

  • Mester P, Wagner M, Rossmanith P (2015) Antimicrobial effects of short chained imidazolium based ionic liquids – influence of anion chaotropicity. Ecotoxicol Environ Saf 111:96–101

    Article  CAS  PubMed  Google Scholar 

  • Osset-Trénor P, Pascual-Ahuir A, Proft M (2023) Fungal drug response and antimicrobial resistance. J Fungi 9(5):565

    Article  Google Scholar 

  • Pendleton JN, Gilmore BF (2015) The antimicrobial potential of ionic liquids: a source of chemical diversity for infection and biofilm control. Int J Antimicrob Agents 46:131–139

    Article  CAS  PubMed  Google Scholar 

  • Pereira FO, Mendes JM, Lima EO (2013) Investigation on mechanism of antifungal activity of eugenol against Trichophyton rubrum. Med Mycology 51:507–513

    Article  CAS  Google Scholar 

  • Rabaan AA, Sulaiman T, Al-Ahmed SH, Buhaliqah ZA, Buhaliqah AA, AlYuosof B, Alfaresi M, Al Fares MA, Alwarthan S, Alkathlan MS et al (2023) Potential strategies to control the risk of antifungal resistance in humans: a comprehensive review. Antibiotics 12(3):608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ranjan P, Kitawat BS, Singh M (2014) 1-Butylimidazole-derived ionic liquids: synthesis, characterisation and evaluation of their antibacterial, antifungal and anticancer activities. RSC Adv 4(96):53634–53644

    Article  CAS  Google Scholar 

  • Ranjan P, Athar M, Vijayakrishna K, Meena LK, Vasita R, Jha PC (2018a) Deciphering the anthelmintic activity of benzimidazolium salts by experimental and in-silico studies. J Mol Liq 268:156–168

    Article  CAS  Google Scholar 

  • Ranjan P, Athar M, Rather H, Vijayakrishna K, Vasita R, Jha PC (2018b) Appraisal of 1-Butylimidazole-derived ionic liquids as anthelmintic agents: an experimental and in silico approach. ChemistrySelect 3(26):7518–7526

    Article  CAS  Google Scholar 

  • Ranjan P, Athar M, Rather H, Vijayakrishna K, Vasita R, Jha PC (2018c) Rational design of imidazolium based salts as anthelmintic agents. J Mol Liq 255:578–588

    Article  CAS  Google Scholar 

  • Riduan SN, Zhang Y (2013) Imidazolium salts and their polymeric materials for biological applications. Chem Soc Rev 42(23):9055–9070

    Article  CAS  PubMed  Google Scholar 

  • Sadeghi A, Jasour AM, Kowsari E, Gheibi M, Ghasemi MH, Ramakrishna S (2024) Comprehensive viewpoint on ionic liquids applications in sustainable pharmaceutical technology (experiments, simulations, and managerial insights). J Mol Liq 11:124991

    Article  Google Scholar 

  • Schrekker HS, Donato RK, Fuentefria AM, Bergamo V, Oliveirac LF, Machadoc MM (2013) Imidazolium salts as antifungal agents: activity against emerging yeast pathogens, without human leukocyte toxicity. Med Chem Comm 11:1457

    Article  Google Scholar 

  • Sikorski RS, Hieter P (1989) A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122:9–27

    Article  Google Scholar 

  • Sivapragasam M, Moniruzzaman M, Goto M (2020) An overview on the toxicological properties of ionic liquids toward microorganisms. Biotech J 15(4):1900073

    Article  CAS  Google Scholar 

  • Sokolova M, Lapalme G (2009) A systematic analysis of performance measures for classification tasks. Inf Proc Management 45(4):427–437

    Article  Google Scholar 

  • Trush MM, Semenyuta IV, Hodyna D, Ocheretniuk AD, Vdovenko SI, Rogalsky SP, Kalashnikova LE, Blagodatnyi V, Kobzar OL, Metelytsia LO (2020) Functionalized imidazolium-based ionic liquids: biological activity evaluation, toxicity screening, spectroscopic, and molecular docking studies. Med Chem Res 29:2181–2191

    Article  CAS  Google Scholar 

  • Venkata Nancharaiah Y, Kiran Kumar Reddy G, Lalithamanasa P, Venugopalan VP (2012) The ionic liquid 1-alkyl-3-methylimidazolium demonstrates comparable antimicrobial and antibiofilm behavior to a cationic surfactant. Biofouling 28:1141–1149

    Article  CAS  PubMed  Google Scholar 

  • Vitiello A, Ferrara F, Boccellino M, Ponzo A, Cimmino C, Comberiati E, Zovi A, Clemente S, Sabbatucci M (2023) Antifungal drug resistance: an emergent health threat. Biomedicines 11(4):1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y, Nie Y (2011) Toxicity and antimicrobial activities of ionic liquids with halogen anion. J Environ Prot 2:298–303

    Article  CAS  Google Scholar 

  • Zhang CW, Zhong XJ, Zhao YS, Rajoka MSR, Hashmi MH, Zhai P, Song X (2023) Antifungal natural products and their derivatives: a review of their activity and mechanism of actions. Pharm Res 7:100262

    Google Scholar 

  • Zhu P, Li Y, Guo T, Liu S, Tancer RJ, Hu C, Zhao C, Xue C, Liao G (2023) New antifungal strategies: drug combination and co-delivery. Advanced Drug Deliv Rev 198:114874

    Article  CAS  Google Scholar 

Download references

Funding

No funding was received.

Author information

Authors and Affiliations

  1. Department of Bioengineering, Gebze Technical University, 41400, Kocaeli, Turkey

    Bengü ERGÜDEN & Fatih TARLAK

  2. Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey

    Yasemin ÜNVER

Authors
  1. Bengü ERGÜDEN
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatih TARLAK
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasemin ÜNVER
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.Ü. synthesized the compounds 1–7, F.T. and B.E. designed and performed the experiments. Y.Ü., F.T. and B.E. wrote the manuscript.

Corresponding author

Correspondence to Bengü ERGÜDEN.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Communicated by Yusuf Akhter.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 1033 KB)

Supplementary file2 (DOCX 142 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

ERGÜDEN, B., TARLAK, F. & ÜNVER, Y. Imidazolium-based ionic liquids disrupt saccharomyces cerevisiae cell membrane integrity. Arch Microbiol 206, 334 (2024). https://doi.org/10.1007/s00203-024-04043-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00203-024-04043-y

Keywords

Search

Navigation