Antimalarial Mannoxanes: Hybrid Antimalarial Drugs with Outstanding Oral Activity Profiles and A Potential Dual Mechanism of Action

Abstract

A double-edged sword! A series of drug hybrids (mannoxanes) have been designed that have the capacity to target Plasmodium falciparum by two distinctive mechanisms. Selected compounds are active at low nanomolar concentrations and outperform artesunate, RKA 182 and a peroxide/amodiaquine combination in terms of curative effects in mice at 10 mg kg−1. Proof of dual mechanism potential is provided by studies on hematin (FeIIIPPIX) dimerisation inhibition and ferrous-mediated, C-centred radical production. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.