Last Updated: 22/12/2025
Design, synthesis and antimalarial activity evaluation of novel small molecule inhibitors targeting Plasmodium falciparum DHODH
Objectives
This project is trying to identify one or two promising lead compounds, which provide theoretic and experimental basis for developing antimalarial drugs with high potency, low toxicity, good specificity and independent intellectual property rights.
Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) has been regarded as an attractive target for the treatment of malaria. In the previous work, a promising hit compound (AM04) with a novel 3,5-disubstituted-1,2,4-triazole scaffold was identified by a ligand- and structure-based virtual screening. Here in, rational drug design, virtual ADME evaluation and molecular docking are utilized for structural optimization and modification of AM04 focusing on core, 3-easter group and 5-aryl. A series of 3,5-disubstituted-1,2,4-triazole derivatives and analogues will be synthesized. Target compounds will be tested and evaluated for their PfDHODH inhibitory activity, species-specificity over human DHODH and in vitro antimalarial activity against FCC-1 strain. 3D-QSAR models (CoMFA and CoMSIA) will be built and structure-activity relationships will be discussed carefully. Potential leads will be evaluated by in vivo murine P. berghei efficacy model.
Jan 2016 — Dec 2018
$31,467
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