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© Artur Scherf
Scanning Electron Microscopy of Red Blood Cell infected by Plasmodium falciparum.
Publication : Journal of medicinal chemistry

Triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors with potent and selective activity against the malaria parasite Plasmodium falciparum

Team: Biology of Host-parasite Interactions
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of medicinal chemistry - 04 Jun 2008

Phillips MA, Gujjar R, Malmquist NA, White J, El Mazouni F, Baldwin J, Rathod PK

Link to Pubmed [PMID] – 18522386

J. Med. Chem. 2008 Jun;51(12):3649-53

A Plasmodium falciparum dihydroorotate dehydrogenase ( PfDHODH) inhibitor that is potent ( KI = 15 nM) and species-selective (>5000-fold over the human enzyme) was identified by high-throughput screening. The substituted triazolopyrimidine and its structural analogues were produced by an inexpensive three-step synthesis, and the series showed good association between PfDHODH inhibition and parasite toxicity. This study has identified the first nanomolar PfDHODH inhibitor with potent antimalarial activity in whole cells (EC50 = 79 nM).