Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/3648
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dc.contributor.authorWezena, C. A.-
dc.contributor.authorUrscher, M.-
dc.contributor.authorVince, R.-
dc.contributor.authorMore, S. S.-
dc.contributor.authorDeponte, M.-
dc.date.accessioned2022-06-27T15:30:58Z-
dc.date.available2022-06-27T15:30:58Z-
dc.date.issued2016-
dc.identifier.issn2213-2317-
dc.identifier.urihttp://hdl.handle.net/123456789/3648-
dc.description.abstractGlyoxalases prevent the formation of advanced glycation end products by converting glycolysis-derived methylglyoxal to D-lactate with the help of glutathione. Vander Jagt and colleagues previously showed that erythrocytes release about thirty times more D-lactate after infection with the human malaria parasite Plasmodium falciparum. Functional glyoxalases in the host-parasite unit might therefore be crucial for parasite survival. Here, we determined the antimalarial and hemolytic activity of two tight binding glyoxalase inhibitors using infected and uninfected erythrocytes. In addition, we synthesized and analyzed a set of diester derivates of both tight-binding inhibitors resulting in up to threefold lower IC50 values and an altered methemoglobin formation and hemolytic activity depending on the type of ester. Inhibitor treatments of uninfected erythrocytes revealed an extremely slow inactivation of the host cell glyoxalase, irrespective of inhibitor modifications, and a potential dispensability of the host cell enzyme for parasite survival. Our study highlights the benefits and drawbacks of different esterifications of glutathione-derived inhibitors and demonstrates the suitability of glyoxalase inhibitors as a tool for deciphering the relevance and mode of action of different glyoxalase systems in a host-parasite unit.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesVol. 8;-
dc.subjectGlyoxalaseen_US
dc.subjectInhibitoren_US
dc.subjectRedoxen_US
dc.subjectPharmacokineticsen_US
dc.subjectErythrocyteen_US
dc.subjectMalariaen_US
dc.titleHEMOLYTIC AND ANTIMALARIAL EFFECTS OF TIGHT-BINDING GLYOXALASE 1 INHIBITORS ON THE HOST-PARASITE UNIT OF ERYTHROCYTES INFECTED WITH PLASMODIUM FALCIPARUMen_US
dc.typeArticleen_US
Appears in Collections:School of Medicine and Health Sciences



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