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The purine salvage pathway offers potential enzyme targets for novel antimalarial agents. Blocking the pathway by which adenosine obtained from the host cell is converted to the purine nucleotides required for nucleic acid synthesis is likely to be highly detrimental to parasite survival. Research has been carried out into finding inhibitors for the first two enzymes in the pathway. Coformycins have been identified as inhibitors of adenosine deaminase, while immucillins inhibit purine nucleoside phosphorylases. However, there has been far greater research into developing inhibitors against the third enzyme in the pathway—hypoxanthine-guanine-[xanthine] phosphoribosyl transferase. These studies have mostly focused on the design of phosphonate, bisphosphonate, and aza bisphosphonate inhibitors, as well as relevant phosphoramidate prodrugs. Some immucillins have also been shown to act as inhibitors. By contrast, little research has been carried out to develop inhibitors for the final two enzymes adenylosuccinate synthase and adenylosuccinate lyase. Investigators have also looked into the possibility of developing antimalarial agents that will block the de novo synthesis of pyrimidines and pyrimidine nucleotides. The greatest level of interest has been in finding inhibitors against orotidine 5’-monophosphate decarboxylase. There has also been interest in blocking deoxyuridine triphosphate nucleotidohydrolase as it plays an important role in controlling levels of dUTP in the parasite cell.

Malaria is a very ancient disease. In the past it occurred across much of the globe, inflicting a heavy burden of morbidity and mortality on affected populations. It remains endemic in much of the tropics and climate change could lead to its resurgence in regions which are currently malaria-free. The first effective treatment, an extract of the bark of the South American cinchona tree, was introduced to Europe by the Jesuits in the 17th century. The discovery of the malaria parasite in the late 19th century was followed by identification of the anopheles mosquito as vector. Understanding of the life cycles of parasites and vectors then led to improvements in disease control. Quinine, the active principle of cinchona, was isolated in the 19th century and remained the unrivalled malaria treatment until the 1940s. Many advances were made in the development of synthetic drugs and insecticides during the World War II, leading to the belief that complete eradication of malaria was an achievable goal. However, the subsequent evolution of drug-resistant parasites and insecticide-resistant mosquitoes led to the resurgence of malaria in areas where it had been controlled. Resistance remains a major challenge, and new drugs, treatment regimens, and vector control methods are urgently required due to the evolution of strains of malaria parasites resistant to all available treatments.