Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate
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Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N′-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.
KeywordsImidazole derivatives Nanohydroxyapatite Candida albicans biofilm Candida krusei biofilm Cytocompatibility
The authors are thankful to Fundação Fernando Pessoa for providing the facilities and financial support and to Fluidinova S.A. for the supply of NanoXIM. This research was also funded by FCT – Fundação para a Ciência e Tecnologia, through UID/MULTI/4546/2019 project, PhD grant SFRH/BD/72866/2010, Chemistry Research Centre of the University of Minho (UID/QUI/00686/2016 e UID/QUI/00686/2018), University of Minho, and Grant Nos. PTDC/SAU-BMA/111233/2009, whose financial support is acknowledged.
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Conflict of interest
The authors declare that they have no conflict of interest.
Neither human participants nor animals were used in this research.