Synthesis of new imidazole-based ionic liquids with antifungal activity against Candida albicans
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Abstract
Background and Objectives: Candida albicans cause a problematic condition in immunocompromised patients that could not be treated quickly due to the resistant behavior of microorganisms. This study aimed to investigate the effect of a novel ionic liquid (IL) as a new drug on C. albicans strains.
Materials and Methods: Seven newly binary ionic liquids mixtures were synthesized, and among them, ([prollinium chloride] [1-methylimidazolium 3-sulfonate] ([pro-HCl][MImS]) was selected and characterized by 1HNMR, 13C NMR, and FT-IR methods. Samples from patients (n=50) with candidiasis were collected and identified through culture media. ERG11 gene overexpression was related to resistance against azole-bearing drugs. The antibiogram, well diffusion assay, MICs, and MFCs tests were operated. PCR and Real-time evaluated the expression of the ERG11 gene, and the rate of cell death was detected using Flow Cytometry.
Results: Our data manifested that this novel IL (Ionic Liquid) can inhibit C. albican's growth, reduce the expression of ERG11 and increase dead cells.
Conclusion: The newly synthesized IL had an inhibiting effect on the growth of the C. albicans strains and may be used as an alternative candidate for novel drug design.
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12. Wang D, An N, Yang Y, Yang X, Fan Y, Feng J. Candida tropicalis distribution and drug resistance is correlated with ERG11 and UPC2 expression. Antimicrob Resist Infect Control 2021; 10: 54.
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14. Jung P, Mischo CE, Gunaratnam G, Spengler C, Becker SL, Hube B, et al. Candida albicans adhesion to central venous catheters: Impact of blood plasma-driven germ tube formation and pathogen-derived adhesins. Virulence 2020; 11: 1453-1465.
15. Eslami M, Ezabadi A, Bayat M, Omidi B, Mortazavi P. Investigation the effect of [Met-Hcl][Pys] ionic liquid on Candida albicans standard strain and evaluation of its toxicity on mammalian cells. Int J Mol Clin Microbiol 2021; 11: 1509-1514.
16. Jeon S, Shin JH, Lim HJ, Choi MJ, Byun SA, Lee D, et al. Disk diffusion susceptibility testing for the rapid detection of fluconazole resistance in Candida isolates. Ann Lab Med 2021; 41: 559-567.
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19. Iyer KR, Robbins N, Cowen LE. Flow cytometric measurement of efflux in Candida species. Curr Protoc Microbiol 2020; 59(1): e121.
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22. Maheronnaghsh M, Teimoori A, Dehghan P, Fatahinia M. The evaluation of the overexpression of the ERG-11, MDR-1, CDR-1, and CDR-2 genes in fluconazole-resistant Candida albicans isolated from Ahvazian cancer patients with oral candidiasis. J Clin Lab Anal 2022; 36(2): e24208.
23. Kiran Kumar Reddy G, Nancharaiah YV. Alkylimidazolium ionic liquids for biofilm control: Experimental studies on controlling multispecies biofilms in natural waters. J Mol Liq 2021; 336: 116859.
24. Gonçalves ARP, Paredes X, Cristino AF, Santos FJV, Queirós CSGP. Ionic liquids-a review of their toxicity to living organisms. Int J Mol Sci 2021; 22: 5612.
25. Samimi M, Hojatnia A. Lactic-based novel amine ionic liquid: synthesis and characterization of [DEA][Lac]. J Chem Pet Eng 2019; 53: 169-176.
26. Busetti A, Crawford DE, Earle MJ, Gilea MA, Gilmore BF, Gorman SP, et al. Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids. Green Chem 2010; 12: 420-425.
27. Dimitrić N, Spremo N, Vraneš M, Belić S, Karaman M, Kovačević S, et al. New protic ionic liquids for fungi and bacteria removal from paper heritage artefacts. RSC Adv 2019; 9: 17905-17912.
28. Yang DD, Paterna NJ, Senetra AS, Casey KR, Trieu PD, Caputo GA, et al. Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy. iScience 2020; 24: 101853.
29. Asghari A, Naghsh N, Madani M. In vitro comparison of antifungal effect of silver nanoparticle on Candida producer of vulvovaginal candidiasis. Iran J Med Microbiol 2015; 9: 23-30.
30. Feng L-j, Wan Z, Wang X-h, Li R-y, Liu W. Relationship between antifungal resistance of fluconazole resistant Candida albicans and mutations in ERG11 gene. Chin Med J (Engl) 2010; 123: 544-548.
31. Jing C-Q, Liu Y-T, Shen X-Y, Li L, Gao Q-Y, Yu Y. Toxic evaluation of the alkylmethylimidazolium-based ionic liquids in yeast Saccharomyces cerevisiae by flow cytometry. Toxin Rev 2012; 31: 27-31.
32. Bleichrodt R-J, Read ND. Flow cytometry and FACS applied to filamentous fungi. Fungal Biol Rev 2019; 33: 1-15.
2. Kuczak M, Musiał M, Malarz K, Rurka P, Zorębski E, Musioł R, et al. Anticancer potential and through study of the cytotoxicity mechanism of ionic liquids that are based on the trifluoromethanesulfonate and bis(trifluoromethylsulfonyl)imide anions. J Hazard Mater 2022; 427: 128160.
3. Fang Z, Zheng X, Li L, Qi J, Wu W, Lu Y. Ionic liquids: emerging antimicrobial agents. Pharm Res 2022; 39: 2391-2404.
4. Moneer EA, Bakr BA, Akl SH, Shahin YH, Elwakil BH, Hagar M, et al. Design and synthesis of novel bis-pyridinium based-ionic liquids as potent antiparasitic agents. Heliyon 2023; 9(4): e15431.
5. Singh SK, Savoy AW. Ionic liquids synthesis and applications: An overview. J Mol Liq 2020; 297: 112038.
6. Hough-Troutman WL, Smiglak M, Griffin S, Reichert WM, Mirska I, Jodynis-Liebert J, et al. Ionic liquids with dual biological function: sweet and anti-microbial, hydrophobic quaternary ammonium-based salts. New J Chem 2009; 33: 26-33.
7. Navale GR, Dharne MS, Shinde SS. Antibiofilm activity of tert-BuOH functionalized ionic liquids with methylsulfonate counteranions. RSC Adv 2015; 5: 68136-68142.
8. Al Kaisy GM, Mutalib MIA, Leveque JM, Rao TVV. Novel low viscosity ammonium-based ionic liquids with carboxylate anions: Synthesis, characterization, and thermophysical properties. J Mol Liq 2017; 230: 565-573.
9. Chaves F, Garnacho-Montero J, Del Pozo JL, Bouza E, Capdevila JA, de Cueto M, et al. Diagnosis and treatment of catheter-related bloodstream infection: Clinical guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology and (SEIMC) and the Spanish Society of Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC). Med Intensiva (Engl Ed) 2018; 42: 5-36.
10. Fu J, Blaylock M, Wickes CF, Welte W, Mehrtash A, Wiederhold N, et al. Development of a Candida glabrata dominant nutritional transformation marker utilizing the Aspergillus nidulans acetamidase gene (amdS). FEMS Yeast Res 2016; 16: fow023.
11. Paul S, Dadwal R, Singh S, Shaw D, Chakrabarti A, Rudramurthy SM, et al. Rapid detection of ERG11 polymorphism associated azole resistance in Candida tropicalis. PLoS One 2021; 16(1): e0245160.
12. Wang D, An N, Yang Y, Yang X, Fan Y, Feng J. Candida tropicalis distribution and drug resistance is correlated with ERG11 and UPC2 expression. Antimicrob Resist Infect Control 2021; 10: 54.
13. Marathe A, Zhu Y, Chaturvedi V, Chaturvedi S. Utility of CHROMagar™ Candida Plus for presumptive identification of Candida auris from surveillance samples. Mycopathologia 2022; 187: 527-534.
14. Jung P, Mischo CE, Gunaratnam G, Spengler C, Becker SL, Hube B, et al. Candida albicans adhesion to central venous catheters: Impact of blood plasma-driven germ tube formation and pathogen-derived adhesins. Virulence 2020; 11: 1453-1465.
15. Eslami M, Ezabadi A, Bayat M, Omidi B, Mortazavi P. Investigation the effect of [Met-Hcl][Pys] ionic liquid on Candida albicans standard strain and evaluation of its toxicity on mammalian cells. Int J Mol Clin Microbiol 2021; 11: 1509-1514.
16. Jeon S, Shin JH, Lim HJ, Choi MJ, Byun SA, Lee D, et al. Disk diffusion susceptibility testing for the rapid detection of fluconazole resistance in Candida isolates. Ann Lab Med 2021; 41: 559-567.
17. Akhavan M, Foroughifar N, Pasdar H, Bekhradnia A. Green synthesis, biological activity evaluation, and molecular docking studies of aryl alkylidene 2, 4-thiazolidinedione and rhodanine derivatives as antimicrobial agents. Comb Chem High Throughput Screen 2019; 22: 716-727.
18. Espinel-Ingroff A, Fothergill A, Peter J, Rinaldi MG, Walsh TJ. Testing conditions for determination of minimum fungicidal concentrations of new and established antifungal agents for Aspergillus spp.: NCCLS collaborative study. J Clin Microbiol 2002; 40: 3204-3208.
19. Iyer KR, Robbins N, Cowen LE. Flow cytometric measurement of efflux in Candida species. Curr Protoc Microbiol 2020; 59(1): e121.
20. El-Kholy MA, Helaly GF, El Ghazzawi EF, El-Sawaf G, Shawky SM. Analysis of CDR1 and MDR1 gene expression and ERG11 substitutions in clinical Candida tropicalis isolates from Alexandria, Egypt. Braz J Microbiol 2023; 10.1007/s42770-023-01106-y.
21. Tavakoli M, Zaini F, Kordbacheh M, Safara M, Raoofian R, Heidari M. Upregulation of the ERG11 gene in Candida krusei by azoles. Daru 2010; 18: 276-280.
22. Maheronnaghsh M, Teimoori A, Dehghan P, Fatahinia M. The evaluation of the overexpression of the ERG-11, MDR-1, CDR-1, and CDR-2 genes in fluconazole-resistant Candida albicans isolated from Ahvazian cancer patients with oral candidiasis. J Clin Lab Anal 2022; 36(2): e24208.
23. Kiran Kumar Reddy G, Nancharaiah YV. Alkylimidazolium ionic liquids for biofilm control: Experimental studies on controlling multispecies biofilms in natural waters. J Mol Liq 2021; 336: 116859.
24. Gonçalves ARP, Paredes X, Cristino AF, Santos FJV, Queirós CSGP. Ionic liquids-a review of their toxicity to living organisms. Int J Mol Sci 2021; 22: 5612.
25. Samimi M, Hojatnia A. Lactic-based novel amine ionic liquid: synthesis and characterization of [DEA][Lac]. J Chem Pet Eng 2019; 53: 169-176.
26. Busetti A, Crawford DE, Earle MJ, Gilea MA, Gilmore BF, Gorman SP, et al. Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids. Green Chem 2010; 12: 420-425.
27. Dimitrić N, Spremo N, Vraneš M, Belić S, Karaman M, Kovačević S, et al. New protic ionic liquids for fungi and bacteria removal from paper heritage artefacts. RSC Adv 2019; 9: 17905-17912.
28. Yang DD, Paterna NJ, Senetra AS, Casey KR, Trieu PD, Caputo GA, et al. Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy. iScience 2020; 24: 101853.
29. Asghari A, Naghsh N, Madani M. In vitro comparison of antifungal effect of silver nanoparticle on Candida producer of vulvovaginal candidiasis. Iran J Med Microbiol 2015; 9: 23-30.
30. Feng L-j, Wan Z, Wang X-h, Li R-y, Liu W. Relationship between antifungal resistance of fluconazole resistant Candida albicans and mutations in ERG11 gene. Chin Med J (Engl) 2010; 123: 544-548.
31. Jing C-Q, Liu Y-T, Shen X-Y, Li L, Gao Q-Y, Yu Y. Toxic evaluation of the alkylmethylimidazolium-based ionic liquids in yeast Saccharomyces cerevisiae by flow cytometry. Toxin Rev 2012; 31: 27-31.
32. Bleichrodt R-J, Read ND. Flow cytometry and FACS applied to filamentous fungi. Fungal Biol Rev 2019; 33: 1-15.
| Files | ||
| Issue | Vol 15 No 6 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v15i6.14162 | |
| Keywords | ||
| Ionic liquid; Imidazole; Proline; ERG11; Candida albicans | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Habibi A, Bayat M, Omidi B, Ezabadi A, Mortazavi P. Synthesis of new imidazole-based ionic liquids with antifungal activity against Candida albicans. Iran J Microbiol. 2023;15(6):811-820.
