1887

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Volume 66, Issue 12

Chain-length-specific anti- activity of cationic lipo-oxazoles: a new class of quaternary ammonium compounds Free

Abstract

species have become resistant to commonly used anti-fungal drugs like fluconazole and echinocandins. In our screen, a series of quaternary ammonium compounds (QACs) emerged as an alternative treatment choice for drug-resistant infections.

Medium alkyl chain cationic lipo-oxazoles comprising six to thirteen twin carbon chains and a quaternary ammonium unit were synthesized and evaluated for their anti- and biofilm inhibition activity. SEM was performed to visualize membrane distortion.

Heptyl and octyl chain analogues (5c, 6b and 6c) showed promising anti-fungal activity. Compound 5c was active against both fluconazole-sensitive and resistant clinical isolates of as well as non- strains. 5c also inhibited the adhesion of cells to a polystyrene surface and restricted biofilm formation. SEM further confirmed cell membrane distortion by 5c.

A novel class of QACs, called cationic lipo-oxazoles, was tested and found to exhibit anti-fungal activity against planktonic cells as well as biofilms of .

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antifungal activity , biofilm , Candida , cationic lipo-oxazole and drug resistance
© 2017 The Authors
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2017-12-01
2024-04-16
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References

  1. Warnock DW. Fungal diseases: an evolving public health challenge. Med Mycol 2006; 44:697–705 [View Article][PubMed]
     [Google Scholar]
  2. Tanwar J, Das S, Fatima Z, Hameed S. Multidrug resistance: an emerging crisis. Interdiscip Perspect Infect Dis 2014; 2014:1–7 [View Article]
     [Google Scholar]
  3. Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence 2013; 4:119–128 [View Article][PubMed]
     [Google Scholar]
  4. Brand A. Hyphal growth in human fungal pathogens and its role in virulence. Int J Microbiol 2012; 2012:1–11 [View Article][PubMed]
     [Google Scholar]
  5. Low C-Y, Rotstein C. Emerging fungal infections in immunocompromised patients. F1000 Med Rep 2011; 3:14 doi: 10.3410/M3-14 [View Article][PubMed]
     [Google Scholar]
  6. Delaloye J, Calandra T. Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence 2014; 5:161–169 [View Article][PubMed]
     [Google Scholar]
  7. Lewis RE. Polyene antifungal agents. In Comarú Pasqualotto A. (editor) Aspergillosis: From Diagnosis to Prevention Netherlands, Dordrecht: Springer; 2010 pp. 281–305
     [Google Scholar]
  8. Martin MV. The use of fluconazole and itraconazole in the treatment of Candida albicans infections: a review. J Antimicrob Chemother 1999; 44:429–437 [View Article][PubMed]
     [Google Scholar]
  9. Denning DW. Echinocandins: a new class of antifungal. J Antimicrob Chemother 2002; 49:889–891 [View Article][PubMed]
     [Google Scholar]
  10. Lewis RE. Current concepts in antifungal pharmacology. Mayo Clin Proc 2011; 86:805–817 [View Article][PubMed]
     [Google Scholar]
  11. Vandeputte P, Ferrari S, Coste AT. Antifungal resistance and new strategies to control fungal infections. Int J Microbiol 2012; 2012:1–26 [View Article][PubMed]
     [Google Scholar]
  12. Shapiro RS, Robbins N, Cowen LE. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 2011; 75:213–267 [View Article][PubMed]
     [Google Scholar]
  13. Sanguinetti M, Posteraro B, Lass-Flörl C. Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses 2015; 58:2–13 [View Article][PubMed]
     [Google Scholar]
  14. Victoria Castelli M, Gabriel Derita M, Noelí López S. Novel antifungal agents: a patent review (2013 - present). Expert Opin Ther Pat 2017; 27:415–426 [View Article][PubMed]
     [Google Scholar]
  15. Goldman RC, Frost DJ, Capobianco JO, Kadam S, Rasmussen RR et al. Antifungal drug targets: Candida secreted aspartyl protease and fungal wall beta-glucan synthesis. Infect Agents Dis 1995; 4:228–247[PubMed]
     [Google Scholar]
  16. Calderone R, Sun N, Gay-Andrieu F, Groutas W, Weerawarna P et al. Antifungal drug discovery: the process and outcomes. Future Microbiol 2014; 9:791–805 [View Article][PubMed]
     [Google Scholar]
  17. Liu X, Wang D, Yu C, Li T, Liu J et al. Potential antifungal targets against a Candida biofilm based on an enzyme in the arachidonic acid cascade-a review. Front Microbiol 2016; 7:1925 [View Article][PubMed]
     [Google Scholar]
  18. Carmona-Ribeiro AM, de Melo Carrasco LD. Cationic antimicrobial polymers and their assemblies. Int J Mol Sci 2013; 14:9906–9946 [View Article][PubMed]
     [Google Scholar]
  19. McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev 1999; 12:147–179[PubMed]
     [Google Scholar]
  20. Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol 2005; 99:703–715 [View Article][PubMed]
     [Google Scholar]
  21. Vieira DB, Carmona-Ribeiro AM. Cationic lipids and surfactants as antifungal agents: mode of action. J Antimicrob Chemother 2006; 58:760–767 [View Article][PubMed]
     [Google Scholar]
  22. Zhang SK, Song JW, Gong F, Li SB, Chang HY et al. Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity. Sci Rep 2016; 6:27394 [View Article][PubMed]
     [Google Scholar]
  23. Vieira DB, Carmona-Ribeiro AM. Cationic lipids and surfactants as antifungal agents: mode of action. J Antimicrob Chemother 2006; 58:760–767 [View Article][PubMed]
     [Google Scholar]
  24. Chen CZ, Beck-Tan NC, Dhurjati P, van Dyk TK, Larossa RA et al. Quaternary ammonium functionalized poly(propylene imine) dendrimers as effective antimicrobials: structure-activity studies. Biomacromolecules 2000; 1:473–480 [View Article][PubMed]
     [Google Scholar]
  25. Jennings MC, Ator LE, Paniak TJ, Minbiole KP, Wuest WM. Biofilm-eradicating properties of quaternary ammonium amphiphiles: simple mimics of antimicrobial peptides. Chembiochem 2014; 15:2211–2215 [View Article][PubMed]
     [Google Scholar]
  26. Ngyugen H, Mcnamee CE. Determination and comparison of how the chain number and chain length of a lipid affects its interactions with a phospholipid at an air/water interface. J Phys Chem B 2014; 118:5901–5912 [View Article][PubMed]
     [Google Scholar]
  27. Bérubé G. An overview of molecular hybrids in drug discovery. Expert Opin Drug Discov 2016; 11:281–305 [View Article][PubMed]
     [Google Scholar]
  28. Davyt D, Serra G. Thiazole and oxazole alkaloids: isolation and synthesis. Mar Drugs 2010; 8:2755–2780 [View Article][PubMed]
     [Google Scholar]
  29. Kuroyanagi J, Kanai K, Sugimoto Y, Horiuchi T, Achiwa I et al. 1,3-Benzoxazole-4-carbonitrile as a novel antifungal scaffold of β-1,6-glucan synthesis inhibitors. Bioorg Med Chem 2010; 18:7593–7606 [View Article][PubMed]
     [Google Scholar]
  30. Smith AB, Liu Z, Hogan AM, Dalisay DS, Molinski TF. Hemi-phorboxazole a: structure confirmation, analogue design and biological evaluation. Org Lett 2009; 11:3766–3769 [View Article][PubMed]
     [Google Scholar]
  31. Shishido TK, Humisto A, Jokela J, Liu L, Wahlsten M et al. Antifungal compounds from cyanobacteria. Mar Drugs 2015; 13:2124–2140 [View Article][PubMed]
     [Google Scholar]
  32. Bathula SR, Reddy MP, Viswanadham K, Sathyanarayana P, Reddy MS. Access to di- and trisubstituted oxazoles by NBS-mediated oxidative cyclisation of N -acyl amino acid derivatives. European J Org Chem 2013; 2013:4552–4557 [View Article]
     [Google Scholar]
  33. Franz R, Kelly SL, Lamb DC, Kelly DE, Ruhnke M et al. Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Antimicrob Agents Chemother 1998; 42:3065–3072[PubMed]
     [Google Scholar]
  34. Coste AT, Karababa M, Ischer F, Bille J, Sanglard D. TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot Cell 2004; 3:1639–1652 [View Article][PubMed]
     [Google Scholar]
  35. Cals I. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast, Approved Standard-3rd ed. CLSI document M27-A3 Wayne: Clinical and Laboratory Standards Institute; 2008
     [Google Scholar]
  36. Pierce CG, Uppuluri P, Tristan AR, Wormley FL, Mowat E et al. A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing. Nat Protoc 2008; 3:1494–1500 [View Article][PubMed]
     [Google Scholar]
  37. Levitz SM, Diamond RD. A rapid colorimetric assay of fungal viability with the tetrazolium salt MTT. J Infect Dis 1985; 152:938–945 [View Article][PubMed]
     [Google Scholar]
  38. Oddo A, Hansen PR. Hemolytic activity of antimicrobial peptides. Methods Mol Biol 2017; 1548:427–435 [View Article][PubMed]
     [Google Scholar]
  39. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986; 89:271–277[PubMed] [Crossref]
     [Google Scholar]
  40. Kathuria M, Bhattacharjee A, Sashidhara KV, Singh SP, Mitra K. Induction of mitochondrial dysfunction and oxidative stress in Leishmania donovani by orally active clerodane diterpene. Antimicrob Agents Chemother 2014; 58:5916–5928 [View Article][PubMed]
     [Google Scholar]
  41. Nobile CJ, Johnson AD. Candida albicans biofilms and human disease. Annu Rev Microbiol 2015; 69:71–92 [View Article][PubMed]
     [Google Scholar]
  42. Uppuluri P, Pierce CG, López-Ribot JL. Candida albicans biofilm formation and its clinical consequences. Future Microbiol 2009; 4:1235–1237 [View Article][PubMed]
     [Google Scholar]
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Chain-length-specific anti-Candida activity of cationic lipo-oxazoles: a new class of quaternary ammonium compounds
J. Med. Microbiol. 66, 1706 (2017); https://doi.org/10.1099/jmm.0.000610
/content/journal/jmm/10.1099/jmm.0.000610
/content/journal/jmm/10.1099/jmm.0.000610
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