Malaria is an infectious disease caused by protozoa of the genus spp. with approximately 219 million cases in 2017. is main responsible for the most severe form of the disease, cerebral malaria. Despite of public health impacts, chemotherapy against malaria is still limited due to the emergence of drug resistance cases used in monotherapy and combination therapies. Thus, the development of new antimalarial drugs becomes emergency. One way of achieve this goal is to explore essential and/or unique therapeutic targets of the parasite, or at least sufficiently different to ensure selective inhibition. Enoil-ACP reductase (ENR) is a NADH-dependent enzyme responsible for the limiting step of the type II fatty acid biosynthetic pathway (FAS II). Thus, pharmacophore and docking based virtual screening were applied to prioritize molecules for assays against W2 strain. The application of successive filters at OOCC database (=618) resulted in the identification of one molecule (13) (EC = 0.098±0.021μM) with similar biological activity to artemether. The molecule 13 is a typical drug repurposing case due to previous other approved therapeutic uses on Chinese medicine as a non-specific cholinergic antagonist, thus it could be accelerated the drug development process. Additionally, molecular dynamics studies were used to confirm stability of the molecular interactions identified by molecular docking. Thus, representative structures of ENR can be used in a study to propose new derivatives for evaluation of biological activity and . Communicated by Ramaswamy H. Sarma.
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