DefinePK

Abstract

Malaria continues to be a significant worldwide health concern, characterized by a substantial illness burden and fatality rate.  The escalating resistance of Plasmodium falciparum to standard antimalarial medications highlights the pressing need for novel therapeutic approaches.  Dihydrofolate reductase (DHFR) is a prominent therapeutic target in malaria, serving as a crucial enzyme in the folate biosynthesis pathway, which is important for the replication and survival of the parasite's DNA.  Nonetheless, extensive resistance to antifolates such as pyrimethamine has emerged due to point mutations in the dhfr gene.  This has resulted in a revitalized focus on creating innovative DHFR inhibitors that are efficacious against resistant strains.  Recent advancements in medicinal chemistry and structure-based drug design have enabled the identification of novel molecules with enhanced affinity for mutant DHFR variants.  The present review examines malaria incidence, resistance mechanisms, and highlights DHFR as a crucial target for the development of next-generation antimalarials..