Medicinal Chemistry Approaches for the Discovery of Plasmodium Falciparum Dihydroorotate Dehydrogenase Inhibitors as Antimalarial Agents

Abstract

Malaria is a severe human disease and a global health problem because of drug-resistant strains. Drugs reported to prevent the growth of Plasmodium 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. Plasmodium falciparum dihydroorotate dehydrogenase is one such enzyme that is necessary for de novo pyrimidine biosynthesis. This review focuses on various medicinal chemistry approaches used for the discovery and identification of selective P. falciparum dihydroorotate dehydrogenase inhibitors as antimalarial agents. This comprehensive review discusses recent advances in the selective therapeutic activity of distinct chemical classes of compounds as P. falciparum dihydroorotate dehydrogenase inhibitors and antimalarial drugs.

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

“…In our previous work, we have provided the coverage of medicinal aspects of heterocycles as anti-malarial scaffolds published during 2016-2020. [29] In continuation to the ongoing efforts on the synthesis of heterocycles [30][31][32][33][34][35][36] as medicinally important scaffolds [37,38] or anti-malarial agents, [39][40][41][42] the present work provides the detail aspects of all the reported heterocycles reported in 2021 and 2022 for the interest of medicinal chemists working on anti-malarial drug development along with their pharmacophoric features, structure-activity relationships (SAR), potential against multi-drug resistant strains, mode of actions, in silico/ in vitro/ in vivo activity, if reported.…”