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Diphenyl diselenide and its interaction with antifungals against Aspergillus spp

2020-08-25Journal article Restricted access
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dc.contributor.authorMelo, Aryse Martins
dc.contributor.authorPoester, Vanice Rodrigues
dc.contributor.authorTrapaga, Mariana
dc.contributor.authorNogueira, Cristina Wayne
dc.contributor.authorZeni, Gilson
dc.contributor.authorMartinez, Marife
dc.contributor.authorSass, Gabriele
dc.contributor.authorStevens, David A
dc.contributor.authorXavier, Melissa Orzechowski
dc.date.accessioned2021-03-31T15:51:18Z
dc.date.available2021-03-31T15:51:18Z
dc.date.issued2020-08-25
dc.description.abstractGiven the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of diphenyl diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates. An experimental model of invasive aspergillosis in mice was studied, and survival curves were compared between an untreated group and groups treated with 100 mg/kg ITC, or (PhSe)2 in different dosages (10 mg/kg, 50 mg/kg and 100 mg/kg). All Aspergillus non-fumigatus and 50% of A. fumigatus were inhibited by (PhSe)2 in concentrations ≤ 64 µg/ml, with significant differences in MICs between the sections. Synergism or additive effect in the in vitro (PhSe)2 interaction with VRC and CAS was observed against the majority of isolates, and with ITC against the non-fumigatus strains. In addition to the inhibitory interaction, (PhSe)2 was able to add a fungicidal effect to CAS. Survival curves from the systemic experimental aspergillosis model demonstrated that the inoculum caused an acute and lethal infection in mice, and no treatment applied significantly prolonged survival over that of the control group. The results highlight the promising activity of (PhSe)2 against Aspergillus species, but more in vivo studies are needed to determine its potential applicability in aspergillosis treatment.pt_PT
dc.description.abstractLay summary: The activity of diphenyl diselenide (PhSe)2 alone and in combination with itraconazole, voriconazole, and caspofungin, is described against three of the most pathogenic Aspergillus sections. (PhSe)2 may prove useful in therapy of infection in future; further study is required.pt_PT
dc.description.sponsorshipThis study was supported by the International Cooperation Program financed by Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil (CAPES), under the Capes-Print Program and PDSE Program - Finance Code 001.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMed Mycol. 2020 Aug 25;myaa072. doi: 10.1093/mmy/myaa072. Online ahead of print.pt_PT
dc.identifier.doi10.1093/mmy/myaa072pt_PT
dc.identifier.issn1369-3786
dc.identifier.urihttp://hdl.handle.net/10400.18/7613
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Press/ International Society for Human and Animal Mycologypt_PT
dc.relation.publisherversionhttps://academic.oup.com/mmy/advance-article-abstract/doi/10.1093/mmy/myaa072/5897158?redirectedFrom=fulltextpt_PT
dc.subjectAspergilluspt_PT
dc.subjectAnimal Modelpt_PT
dc.subjectAspergillosispt_PT
dc.subjectCheckerboardpt_PT
dc.subjectSeleniumpt_PT
dc.subjectSynergismpt_PT
dc.subjectInfecções Sistémicas e Zoonoses
dc.titleDiphenyl diselenide and its interaction with antifungals against Aspergillus spppt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPagemyaa072pt_PT
oaire.citation.titleMedical Mycologypt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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