In silico screening for Plasmodium falciparum enoyl-ACP reductase inhibitors
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- Lindert, S., Tallorin, L., Nguyen, Q.G. et al. J Comput Aided Mol Des (2015) 29: 79. doi:10.1007/s10822-014-9806-3
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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.