Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates
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- dc.contributor.author Aguiar, Luísa
- dc.contributor.author Biosca, Arnau
- dc.contributor.author Lantero, Elena
- dc.contributor.author Gut, Jiri
- dc.contributor.author Vale, Nuno
- dc.contributor.author Rosenthal, Philip J.
- dc.contributor.author Nogueira, Fátima
- dc.contributor.author Andreu Martínez, David
- dc.contributor.author Fernàndez Busquets, Xavier
- dc.contributor.author Gomes, Paula
- dc.date.accessioned 2020-01-10T08:39:15Z
- dc.date.available 2020-01-10T08:39:15Z
- dc.date.issued 2019
- dc.description.abstract Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates.
- dc.format.mimetype application/pdf
- dc.identifier.citation Aguiar L, Biosca A, Lantero E, Gut J, Vale N, Rosenthal PJ et al. Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates. Molecules. 2019;24(24):e4559. DOI: 10.3390/molecules24244559
- dc.identifier.doi http://dx.doi.org/10.3390/molecules24244559
- dc.identifier.issn 1420-3049
- dc.identifier.uri http://hdl.handle.net/10230/43254
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Molecules. 2019;24(24):e4559
- dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Plasmodium
- dc.subject.keyword Antimalarial
- dc.subject.keyword Cell penetrating peptide
- dc.subject.keyword Chloroquine
- dc.subject.keyword Erythrocyte fluorescence
- dc.subject.keyword Flow cytometry
- dc.subject.keyword Hemolysis
- dc.subject.keyword Microscopy
- dc.subject.keyword Primaquine
- dc.subject.keyword Red blood cell
- dc.title Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion