A Cyclam Salt as an Antifungal Agent: Interference with <i>Candida</i> spp. and <i>Cryptococcus neoformans</i> Mechanisms of Virulence
Fátima Cerqueira,
Rui Medeiros,
Inês Lopes,
Carla Campos,
Maria Pia Ferraz,
Fernando Silva,
Luís G. Alves,
Eugénia Pinto
Affiliations
Fátima Cerqueira
FP-I3ID, FP-BHS, GIT-LoSa, University Fernando Pessoa, Praça 9 de Abril, 349, 4249-004 Porto, Portugal
Rui Medeiros
FP-I3ID, FP-BHS, GIT-LoSa, University Fernando Pessoa, Praça 9 de Abril, 349, 4249-004 Porto, Portugal
Inês Lopes
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
Carla Campos
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
Maria Pia Ferraz
Department of Metallurgical and Materials Engineering, Faculty of Engineering (FEUP), University of Porto (UP), 4200-465 Porto, Portugal
Fernando Silva
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
Luís G. Alves
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
Eugénia Pinto
Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy, University of Porto (UP), Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
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.
