Quinolones: breathing new life into an old class of compounds to tackle malaria

One compound shows potential to cure malaria and block transmission at low doses

20 Mar 2013

Today, Science Translational Medicine publishes details of a series of potent compounds active against malaria with transmission-blocking potential. The 4-(1H)-quinolone-3-diarylethers were discovered by an MMV project team led by Professors Mike Riscoe, at Oregon Health & Science University, and Roman Manetsch, at the University of South Florida, over 60 years after the discovery of endochin – the first antimalarial quinolone.

Endochin was never followed up at the time due to a lack of activity in humans. Today, however, these quinolones have been optimized and demonstrated to be highly active against the blood stages of both major species of malaria parasite (Plasmodium falciparum and Plasmodium vivax). They have also been shown to have excellent liver-stage activity as well as inhibitory effects on the stages that lead to malaria transmission.

These quinolones target the same biological pathway as atovaquone – the main component of the antimalarial, Malarone® (atovaquone/proguanil), but are likely to be much cheaper to produce and have also been shown to be effective against parasite strains that have developed resistance to atovaquone.

One candidate from the series, ELQ-300, has already been selected for preclinical testing. Initial data demonstrates that the compound has impressive prophylactic and transmission-blocking activity, and could form part of a drug combination for a single-dose cure or chemo-protection.

 “ELQ-300 is an exciting compound as it ticks a number of boxes of what we need in a next-generation antimalarial,” said Dr Tim Wells, MMV’s Chief Scientific Officer. “It has potential to become part of a combination therapy that could cure patients, prevent infection and block the transmission of malaria – all at low-doses – which means fewer and smaller pills for patients, at a lower cost. Provided a formulation can be developed, ELQ-300 holds great promise to become a tool to help shrink the malaria map.”    

This collaborative project has drawn on the expertise of scientists from Oregon Health & Science University, the University of South Florida, Drexel University, Monash University, Imperial College of London, Menzies School of Health Research, Griffith University, GSK (Tres Cantos) and MMV.