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

  • C. Gabriel
  • L. GrenhoEmail author
  • F. Cerqueira
  • R. Medeiros
  • A. M. Dias
  • A. I. Ribeiro
  • M. F. Proença
  • M. H. Fernandes
  • J. C. Sousa
  • F. J. Monteiro
  • M. P. Ferraz
Original Article


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.

Graphic Abstract


Imidazole 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.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Neither human participants nor animals were used in this research.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • C. Gabriel
    • 1
  • L. Grenho
    • 1
    • 2
    • 3
    • 4
    • 5
    • 9
    Email author
  • F. Cerqueira
    • 1
    • 6
  • R. Medeiros
    • 1
    • 6
    • 7
  • A. M. Dias
    • 8
  • A. I. Ribeiro
    • 8
  • M. F. Proença
    • 8
  • M. H. Fernandes
    • 5
    • 9
  • J. C. Sousa
    • 1
  • F. J. Monteiro
    • 2
    • 3
    • 4
  • M. P. Ferraz
    • 1
    • 2
    • 3
    • 6
  1. 1.Health Sciences FacultyUniversity Fernando PessoaPortoPortugal
  2. 2.i3S - Instituto de Investigação e Inovação em SaúdeU. PortoPortoPortugal
  3. 3.INEB - Instituto de Engenharia BiomédicaU. PortoPortoPortugal
  4. 4.Departamento de Engenharia Metalúrgica e Materiais, Faculdade de EngenhariaU. PortoPortoPortugal
  5. 5.Laboratory for Bone Metabolism and Regeneration, Faculty of Dental MedicineU. PortoPortoPortugal
  6. 6.FP-ENAS/CEBIMED, Energy, Environment and Health Research Unit/Biomedical Research CenterUniversity Fernando PessoaPortoPortugal
  7. 7.Molecular Oncology GRP and Molecular Biology Laboratory - Virology ServicePortuguese Institute of Oncology (IPO)PortoPortugal
  8. 8.Department of Chemistry, Centre of ChemistryUniversity of MinhoBragaPortugal
  9. 9.REQUIMTE/LAQVU. PortoPortoPortugal

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