Medicinal chemistry approaches for the discovery of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors as antimalarial agents

Malaria is a severe human disease and a global health problem because of drug-resistant strains. Drugs reported to prevent the growth of parasites target various phases of the parasites' life cycle. Antimalarial drugs can inhibit key enzymes that are responsible for the cellular growth and development of parasites. dihydroorotate dehydrogenase is one such enzyme that is necessary for pyrimidine biosynthesis. This review focuses on various medicinal chemistry approaches used for the discovery and identification of selective dihydroorotate dehydrogenase inhibitors as antimalarial agents. This comprehensive review discusses recent advances in the selective therapeutic activity of distinct chemical classes of compounds as dihydroorotate dehydrogenase inhibitors and antimalarial drugs.