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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

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

Journal

Title: Molecules

Vol. 24

Final page: 4559

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 18 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 21