Computational Identification of Dihydroorotate Dehydrogenase Interactive Ligands, Therapeutic Aid for Malaria Parasite

Abstract

This study aims to identify novel inhibitors of dihydroorotate dehydrogenase (DDI) as potential therapeutic agents for malaria. DDIs are crucial in disrupting the Plasmodium life cycle within the human body, and targeting these inhibitors could prevent the proliferation of malaria. We used computational methods to identify the active sites of dihydroorotate dehydrogenase for inhibition. Four bio/organic synthetic molecules were evaluated: comalic acid, 4,4',4''-triaminotriphenylamine, and 6-chloroquinoline-3. Molecular docking studies showed that comalic acid and 4,4',4''-triaminotriphenylamine effectively bind to the enzyme’s active sites, indicating they could be strong DDI inhibitors. In contrast, 6-chloroquinoline-3-carbaldehyde demonstrated lower inhibitory potential, and 2-(3-aminoanilino) phenol exhibited no significant activity. Additionally, the study includes a tabulation of oral toxicity results and chemical properties of the ligands, which provides knowledge about their potential therapeutic safety and efficacy. This information is crucial for guiding future research and development of these compounds as viable therapeutic agents. Further investigations into their mechanisms of action and potential side effects will be essential for optimizing their use in clinical applications.