Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate

Mycopathologia. 2019 Dec;184(6):775-786. doi: 10.1007/s11046-019-00400-4. Epub 2019 Nov 2.

Abstract

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.

Keywords: Candida albicans biofilm; Candida krusei biofilm; Cytocompatibility; Imidazole derivatives; Nanohydroxyapatite.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Biocompatible Materials
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Candida* / drug effects
  • Candida* / growth & development
  • Cell Line / drug effects
  • Humans
  • Imidazoles / pharmacology
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning
  • Osteoblasts / drug effects
  • Prostheses and Implants / microbiology*
  • Prosthesis-Related Infections / drug therapy*
  • Prosthesis-Related Infections / microbiology

Substances

  • Antifungal Agents
  • Biocompatible Materials
  • Imidazoles
  • 4-aminoimidazole