Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Aguiar, L (Autor) Outra; Biosca, A (Autor) Outra; Lantero, E (Autor) Outra; Gut, J (Autor) Outra; Nuno Vale (Autor) ICBAS; Rosenthal, PJ (Autor) Outra; Nogueira, F (Autor) Outra; Andreu, D (Autor) Outra; Fernandez Busquets, X (Autor) Outra; Paula Gomes (Autor) FCUP

Revista

Título: Molecules

Vol. 24

Página Final: 4559

ISSN: 1420-3049

Editora: MDPI

Indexação

ISI Web of Knowledge - 17 Citações

Scopus - 18 Citações

Outras Informações

ID Authenticus: P-00R-GK3

DOI: 10.3390/molecules24244559

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 21