UC San Diego
In silico screening for Plasmodium falciparum enoyl-ACP reductase inhibitors
- Author(s): Lindert, S
- Tallorin, L
- Nguyen, QG
- Burkart, MD
- McCammon, JA
- et al.
Published Web Locationhttp://dx.doi.org/10.1007/s10822-014-9806-3
© 2014 Springer International Publishing Switzerland. The need for novel therapeutics against Plasmodium falciparum is urgent due to recent emergence of multi-drug resistant malaria parasites. Since fatty acids are essential for both the liver and blood stages of the malarial parasite, targeting fatty acid biosynthesis is a promising strategy for combatting P. falciparum. We present a combined computational and experimental study to identify novel inhibitors of enoyl-acyl carrier protein reductase (PfENR) in the fatty acid biosynthesis pathway. A small-molecule database from ChemBridge was docked into three distinct PfENR crystal structures that provide multiple receptor conformations. Two different docking algorithms were used to generate a consensus score in order to rank possible small molecule hits. Our studies led to the identification of five low-micromolar pyrimidine dione inhibitors of PfENR.
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