Anti-Candida albicans biofilm effect of novel heterocyclic compounds

Sarah Kagan, Adel Jabbour, Edward Sionov, Abed A. Alquntar, Doron Steinberg, Morris Srebnik, Ran Nir-paz, Aryeh Weiss, Itzhack Polacheck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Objectives: The aims of this study were to develop new anti-biofilm drugs, examine their activity against Candida albicans biofilm and investigate their structure-activity relationship and mechanism of action. Methods: A series of thiazolidinedione and succinimide derivatives were synthesized and their ability to inhibit C. albicans biofilm formation and destroy pre-formed biofilm was tested. The biofilms' structure, metabolic activity and viability were determined by XTT assay and propidium iodide and SYTO 9 live/dead stains combined with confocal microscopic analysis. The effect of the most active compounds on cell morphology, sterol distribution and cell wall morphology and composition was then determined by specific fluorescent stains and transmission electron microscopy. Results: Most of the compounds were active at sub-MICs. Elongation of the aliphatic side chain resulted in reduced anti-biofilm activity and the sulphur atom contributed to biofilm killing, indicating a structure-activity relationship. The compounds differed in their effects on biofilm viability, yeast-to-hyphal form transition, hyphal morphology, cell wall morphology and composition, and sterol distribution. The most effective anti-biofilm compounds were the thiazolidinedione S8. H and the succinimide NA8. Conclusions: We developed novel anti-biofilm agents that both inhibited and destroyed C. albicans biofilm. With some further development, these agents might be suitable for therapeutic purposes.

Original languageAmerican English
Article numberdkt365
Pages (from-to)416-427
Number of pages12
JournalJournal of Antimicrobial Chemotherapy
Volume69
Issue number2
DOIs
StatePublished - Feb 2014

Bibliographical note

Funding Information:
This work was supported in part by a grant from the Public Committee for AllocationofEstateFunds,MinistryofJustice,Israel(grantnumber3-4123).

Keywords

  • Antifungal
  • C. albicans
  • Quorum sensing
  • TZD

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