Abstract Background: Resistance to existing antifolate drugs targeting the dihydrofolate reductase (DHFR) enzyme in Plasmodium falciparum is a major obstacle to malaria control. Furthermore, some current drugs have associated toxicity concerns. To address this, we explored new antifolate inhibitors to develop safer and more potent antimalarial drugs. Methods: We computationally screened hypothetical compounds A1, A2, and A3 (a parent compound and two alcohol derivatives) for their toxicit...