Antifungal activity of naphthoquinoidal compounds in vitro against fluconazole-resistant strains of different Candida species: a special emphasis on mechanisms of action on Candida tropicalis.

Autor:	Neto JB; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil., da Silva CR; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Pathology and Legal Medicine, School of Medicine, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil., Neta MA; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Pathology and Legal Medicine, School of Medicine, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil., Campos RS; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Pathology and Legal Medicine, School of Medicine, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil., Siebra JT; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil., Silva RA; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil., Gaspar DM; Department of Physiology and Pharmacology, Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil., Magalhães HI; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Pharmaceutical Sciences, Center for Toxicological Assistance, University Federal of Paraíba, Paraíba, Brazil., de Moraes MO; Department of Physiology and Pharmacology, Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil., Lobo MD; Department of Biology, ScienceCenter, Molecular Genetics Laboratory, Federal University of Ceará, Ceará, Brazil., Grangeiro TB; Department of Biology, ScienceCenter, Molecular Genetics Laboratory, Federal University of Ceará, Ceará, Brazil., Carvalho TS; Natural Products Research Nucleus, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Diogo EB; Department of Chemistry, Institute of Exact Sciences, Laboratory of Synthetic and Heterocyclic Chemistry, Federal University of Minas Gerais, Minas Gerais, Brazil., da Silva Júnior EN; Department of Chemistry, Institute of Exact Sciences, Laboratory of Synthetic and Heterocyclic Chemistry, Federal University of Minas Gerais, Minas Gerais, Brazil., Rodrigues FA; Department of Physiology and Pharmacology, Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil., Cavalcanti BC; Department of Pathology and Legal Medicine, School of Medicine, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Physiology and Pharmacology, Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil., Júnior HV; Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Pathology and Legal Medicine, School of Medicine, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Physiology and Pharmacology, Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2014 May 09; Vol. 9 (5), pp. e93698. Date of Electronic Publication: 2014 May 09 (Print Publication: 2014).
DOI:	10.1371/journal.pone.0093698
Abstrakt:	In recent decades, the incidence of candidemia in tertiary hospitals worldwide has substantially increased. These infections are a major cause of morbidity and mortality; in addition, they prolong hospital stays and raise the costs associated with treatment. Studies have reported a significant increase in infections by non-albicans Candida species, especially C. tropicalis. The number of antifungal drugs on the market is small in comparison to the number of antibacterial agents available. The limited number of treatment options, coupled with the increasing frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. The objective of this study was to evaluate and compare the antifungal activities of three semisynthetic naphthofuranquinone molecules against fluconazole-resistant Candida spp. strains. These results allowed to us to evaluate the antifungal effects of three naphthofuranquinones on fluconazole-resistant C. tropicalis. The toxicity of these compounds was manifested as increased intracellular ROS, which resulted in membrane damage and changes in cell size/granularity, mitochondrial membrane depolarization, and DNA damage (including oxidation and strand breakage). In conclusion, the tested naphthofuranquinones (compounds 1-3) exhibited in vitro cytotoxicity against fluconazole-resistant Candida spp. strains.
Databáze:	MEDLINE
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