Recent advances on patents of dihydroorotate dehydrogenase (DHODH) inhibitors as antimalarial agents.

INTRODUCTION

Pyrimidine nucleotides are essential for the parasite's growth and replication. Parasites have only a pathway for the biosynthesis of pyrimidine nucleotides. Dihydroorotate dehydrogenase (DHODH) enzyme is involved in the rate-limiting step of the pyrimidine biosynthesis pathway. DHODH is a biochemical target for the discovery of new antimalarial agents.

AREA COVERED

This review discussed the development of patented DHODH inhibitors published between 2007 and 2023 along with their chemical structures and activities.

EXPERT OPINION

DHODH enzyme is involved in the rate-limiting fourth step of the pyrimidine biosynthesis pathway. Thus, inhibition of DHODH using species-selective inhibitors has drawn much attention for treating malaria because they inhibit parasite growth without affecting normal human functions. Looking at the current scenario of antimalarial drug resistance with most of the available antimalarial drugs, there is a huge need for targeted newer agents. Newer agents with unique mechanisms of action may be devoid of drug toxicity, adverse effects, and the ability of parasites to quickly gain resistance, and DHODH inhibitors can be those newer agents. Many DHODH inhibitors were patented in the past, and the dependency of on pyrimidine provided a new approach for the development of novel antimalarial agents.