Structure-Based Drug Design of PfDHODH Inhibitors as Antimalarial Agents

Abstract

Structure-based drug design (SBDD) is being efficiently used for the design of antimalarial agents. It is a very effective tool for challenges like drug selectivity and resistance. Over the past decade, a considerable number of druggable targets have been explored—these include Na+ ATPase 4 ion channel, cytochrome bc1, mitochondrial electron transport chain, phosphatidylinositol 4-kinase (PfPI4 K), dihydroorotate dehydrogenase, hemozoin formation, dihydrofolate reductase inhibitors, etc. Among these, Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a new and very promising target. PfDHODH has shown considerable potential in arresting growth of the parasite at blood stage by inhibiting pyrimidine biosynthesis. This chapter provides a review of all the SBDD efforts for the development of inhibitors against PfDHODH.