Anti-Candida albicans biofilm effect of novel heterocyclic compounds
| Autor: | Itzhack Polacheck, Morris Srebnik, Ran Nir-Paz, Sarah Kagan, Edward Sionov, Abed Al-Quntar, Adel Jabbour, Doron Steinberg, Aryeh Weiss |
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| Rok vydání: | 2013 |
| Předmět: |
Microbiology (medical)
Antifungal Agents Cell morphology Microbiology Cell wall Structure-Activity Relationship chemistry.chemical_compound Succinimide Heterocyclic Compounds Candida albicans Animals Pharmacology (medical) Propidium iodide Pharmacology Sheep biology Chemistry Biofilm biochemical phenomena metabolism and nutrition biology.organism_classification Sterol Corpus albicans Infectious Diseases Biochemistry Biofilms |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 69:416-427 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | 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 S8H 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. |
| Databáze: | OpenAIRE |
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