Scientists have identified a promising new antimalarial drug which has the potential to cure the mosquito-borne disease, and block its transmission with low doses, in developing countries like India.
An international team of researchers developed a series of potent compounds to combat malaria known as the 4-(1H)-quinolone-3-diarylethers, or quinolones.
The researchers narrowed the most effective drug candidates in the quinolones series to one lead drug - ELQ-300 - now moving toward clinical testing.
In initial preclinical tests, the lead drug demonstrated impressive preventive and transmission-blocking - and a low likelihood for developing rapid resistance to major strains of malaria parasites.
In addition, ELQ-300 could likely be produced more cheaply than existing antimalarial drugs - a major advantage in treating a tropical disease that kills nearly one million people a year and causes recurring bouts of severe and incapacitating illness, most often among poor people in developing countries.
"This is one of the first drugs ever to kill the malaria parasite in all three stages of its life cycle," said Dennis Kyle from the University of South Florida.
"So, it may become part of a new-generation therapy that not only treats sick people and prevents them from getting ill, but also blocks the transmission of malaria from mosquitoes to humans. If the drug can break the parasite life cycle, we may ultimately eradicate the disease," Kyle said.
The new drug class identified by the researchers were derived from the first antimalarial quinolone, endochin, discovered more than 60 years ago but never pursued as a treatment because it appeared not to work in humans.
Using new technology, researchers demonstrated that these compounds were indeed highly effective against Plasmodium falciparum, the most lethal strain of malaria, and Plasmodium vivax, the major cause of malaria outside Africa.
The quinolones target both the liver and blood stages of the parasite as well as the forms critical for disease transmission.
Researchers structurally modified the quinolone scaffold so that the drug candidate ELQ-300 would selectively hit only the malaria parasite's target while sparing the human mitochondria.
The quinolones, including ELQ-300, target the same biological pathway as atovaquone, the main component of Malarone, one of the newest combination drugs used to treat malaria. But, in repeated experiments ELQ-300 did not generate drug-resistant strains of the malaria parasite - making it a significant improvement over atovaquone.
The study included researchers from Oregon Health & Science University in Portland, Drexel University in Philadelphia, and Monash University in Australia.
The findings were published in the journal Science Translational Medicine.
