Publication:
Assessment of the Activity of Decoquinate and Its Quinoline-O-Carbamate Derivatives against Toxoplasma gondii In Vitro and in Pregnant Mice Infected with T. gondii Oocysts

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dc.contributor.authorRamseier, Jessica
dc.contributor.authorImhof, Dennis
dc.contributor.authorAnghel, Nicoleta
dc.contributor.authorHänggeli, Kai Pascal Alexander
dc.contributor.authorBeteck, Richard M.
dc.contributor.authorBalmer, Verena
dc.contributor.authorOrtega-Mora, Luis-Miguel
dc.contributor.authorSanchez-Sanchez, Roberto
dc.contributor.authorFerre, Ignacio
dc.contributor.authorHaynes, Richard K.
dc.contributor.authorHemphill, Andrew
dc.date.accessioned2024-10-05T06:56:33Z
dc.date.available2024-10-05T06:56:33Z
dc.date.issued2021
dc.description.abstractAbstract: The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacterial and parasitic infections, most notably, coccidiosis in poultry and in ruminants. We have investigated the effects of treatment of Toxoplasma gondii in infected human foreskin fibroblasts (HFF) with DCQ. This induced distinct alterations in the parasite mitochondrion within 24 h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect. Based on the low half-maximal effective concentration (IC50) of 1.1 nM and the high selectivity index of >5000, the efficacy of oral treatment of pregnant mice experimentally infected with T. gondii oocysts with DCQ at 10 mg/kg/day for 5 days was assessed. However, the treatment had detrimental effects, induced higher neonatal mortality than T. gondii infection alone, and did not prevent vertical transmission. Thus, three quinoline-O-carbamate derivatives of DCQ, anticipated to have better physicochemical properties than DCQ, were assessed in vitro. One such compound, RMB060, displayed an exceedingly low IC50 of 0.07 nM, when applied concomitantly with the infection of host cells and had no impact on HFF viability at 10 µM. As was the case for DCQ, RMB060 treatment resulted in the alteration of the mitochondrial matrix and loss of cristae, but the changes became apparent at just 6 h after the commencement of treatment. After 48 h, RMB060 induced the expression of the bradyzoite antigen BAG1, but TEM did not reveal any other features reminiscent of bradyzoites. The exposure of infected cultures to 300 nM RMB060 for 52 days did not result in the complete killing of all tachyzoites, although mitochondria remained ultrastructurally damaged and there was a slower proliferation rate. The treatment of mice infected with T. gondii oocysts with RMB060 did reduce parasite burden in non-pregnant mice and dams, but vertical transmission to pups could not be prevented.
dc.description.sponsorshipInstitut für Parasitologie (IPA)
dc.identifier.doi10.48350/160680
dc.identifier.publisherDOI10.3390/molecules26216393
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/54095
dc.language.isoen
dc.publisherMDPI
dc.relation.ispartofMolecules
dc.relation.issn1420-3049
dc.relation.organizationDCD5A442BFE6E17DE0405C82790C4DE2
dc.relation.organization5EBDFFD4994748B4B44FD17D5E463CFB
dc.relation.schoolDCD5A442C27BE17DE0405C82790C4DE2
dc.subject.ddc500 - Science
dc.subject.ddc500 - Science::570 - Life sciences; biology
dc.subject.ddc500 - Science::590 - Animals (Zoology)
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.subject.ddc600 - Technology::630 - Agriculture
dc.titleAssessment of the Activity of Decoquinate and Its Quinoline-O-Carbamate Derivatives against Toxoplasma gondii In Vitro and in Pregnant Mice Infected with T. gondii Oocysts
dc.typearticle
dspace.entity.typePublication
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oaire.citation.issue21
oaire.citation.startPage6393
oaire.citation.volume26
oairecerif.author.affiliationInstitut für Parasitologie (IPA)
oairecerif.author.affiliationInstitut für Parasitologie (IPA)
oairecerif.author.affiliationInstitut für Parasitologie (IPA)
oairecerif.author.affiliationInstitut für Parasitologie (IPA)
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oairecerif.author.affiliationInstitut für Parasitologie (IPA)
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unibe.date.licenseChanged2021-11-10 09:59:21
unibe.description.ispublishedpub
unibe.eprints.legacyId160680
unibe.journal.abbrevTitleMOLECULES
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unibe.subtype.articlejournal

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