Ferroquine-derived polyamines that target resistant Plasmodium falciparum

Tameryn Stringer, Lubbe Wiesner, Gregory S. Smith

Research output: Contribution to journalArticlepeer-review

16 Citations (SciVal)

Abstract

Rising resistance to conventional therapies for malaria has led to the search for novel drugs and strategies with distinct mechanisms of action that may overcome this. Ferroquine is currently the gold standard as far as antimalarial metal-based drugs are concerned and is currently in phase IIb clinical trials as part of the MMV pipeline (in partnership with Sanofi) of antimalarials. It is assumed to inhibit haemozoin formation like chloroquine and maintain its activity in the resistant strain. Here we report two ferroquine-derived polyamines that target a resistant strain of Plasmodium falciparum. Furthermore, upon treatment of Plasmodium falciparum with a ferroquine-derived polyamine, cellular haem fractionation experiments reveal that the inhibition of haemozoin formation is likely not the mechanism responsible for their activity, an important result to aid further clinical development.
Original languageEnglish
Pages (from-to)78-83
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume179
Early online date8 Jun 2019
DOIs
Publication statusPublished - 1 Oct 2019

Cite this