Folate metabolism in human malaria parasites--75 years on.

摘要: Malaria still poses one of the most serious threats to human health worldwide and prevailing lack effective, clinically licensed, vaccines means that prophylaxis treatment depend heavily on a small number compounds whose efficacies are progressively compromised at varying rates by inevitable emergence drug-resistant parasite populations. Of these antimalarials, those inhibiting steps in folate metabolism, along with chloroquine, oldest synthetic compounds, origins dating back three-quarters century. Despite widespread resistance, antifolates play an important role malaria control, our understanding underlying mechanisms metabolism genesis drug resistance has increased considerably over last twenty years. Folate de novo synthesis parasite, interconversion active derivatives their utilisation as multifunctional cofactors involve numerous enzymes, although only two have ever served targets clinical antimalarial inhibitors. The current application antifolates, this class drugs, new insights into its potential for providing novel inhibition some questions outstanding reviewed here.