Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one.
According to the World Health Organisation, approximately 212 million people suffered from malaria in 2015 and some 438,000 of them didn’t survive.1P. falciparum causes the most severe malarial disease and is the leading cause of death in Africa. Increasing resistance to antimalarial drugs, diminishing their therapeutic efficacy, presents a major barrier to disease management.
To date, over 70 analogues of 3-methyl-4-cyanoisoquinoline have been synthesised to determine the structure-activity relationships of this class of compounds against P. falciparum. Most recently, we have identified the biological target and have confirmed nanomolar potency. These encouraging results suggest these isoquinolines may be suitable for consideration as new therapeutics for the treatment of malaria.