A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence

Author:

Cerqueira Fátima123ORCID,Medeiros Rui123ORCID,Lopes Inês34,Campos Carla3,Ferraz Maria Pia567ORCID,Silva Fernando89ORCID,Alves Luís G.10ORCID,Pinto Eugénia1112ORCID

Affiliation:

1. FP-I3ID, FP-BHS, GIT-LoSa, University Fernando Pessoa, Praça 9 de Abril, 349, 4249-004 Porto, Portugal

2. Faculty of Health Sciences, University Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal

3. Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal

4. School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal

5. Department of Metallurgical and Materials Engineering, Faculty of Engineering (FEUP), University of Porto (UP), 4200-465 Porto, Portugal

6. i3S—Institute for Research and Innovation in Health, University of Porto (UP), 4099-002 Porto, Portugal

7. Institute of Biomedical Engineering (INEB), University of Porto (UP), 4099-002 Porto, Portugal

8. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal

9. REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal

10. Centro de Química Estrutural—Institute of Molecular Sciences, Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento, Av. António José de Almeida nº12, 1000-043 Lisboa, Portugal

11. Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy, University of Porto (UP), Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal

12. CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, 4450-208 Matosinhos, Portugal

Abstract

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

Funder

national funds of FCT/MCTES—Foundation for Science and Technology I.P. from the Ministry of Science, Technology, and Higher Education

European Regional Development Fund (ERDF) by the COMPETE—Programa Operacional Factores de Competitividade

Group of Marine Natural Products and Medicinal Chemistry CIIMAR

Research Center of the Portuguese Oncology Institute of Porto

FCT projects

Publisher

MDPI AG

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