Identification of Flavonoids as Inhibitors of Plasmodium falciparum Enoyl-ACP Reductase by Hierarchical Virtual Screening

Malaria, a parasitic infection caused by Plasmodium falciparum, is a serious global public health problem. The enzyme enoyl-acyl carrier protein (ACP) reductase present in a limiting step in the biosynthesis of fatty acids type II was used to search for novel molecules with potential inhibitor by virtual screening techniques. A flavonoid library obtained in ChEMBL database (n = 4,008) was filtered through physico-chemical similarity using the Euclidean distance as a criterion. The selected molecules were subjected to molecular docking using the scoring function GridScore in the DOCK 6.5 software. The top 30 ranked molecules by molecular docking were submitted to the AuPosSOM 2.1 software with the aim of clustering molecules by means of intermolecular interactions in order to understand the patterns of these interactions with enoyl-ACP reductase from Plasmodium falciparum (PfENR). We observed the importance of flavonoid moiety to hydrophobic interactions with the active site of enzyme, this confirmed the choice to study this metabolite class as PfENR inhibitors. Moreover, it was possible to recognize which intermolecular interactions contribute to the molecular recognition process.