Anti-Candida albicans biofilm effect of novel heterocyclic compounds.
OBJECTIVE
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.
Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, Israel.
Sarah
S
Kagan
Adel
A
Jabbour
Edward
E
Sionov
Abed A
AA
Alquntar
Doron
D
Steinberg
Morris
M
Srebnik
Ran
R
Nir-Paz
Aryeh
A
Weiss
Itzhack
I
Polacheck
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D012756:Sheep; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D006571:Heterocyclic Compounds
C. albicans; TZD; antifungal; quorum sensing