title: Combined 3D-QSAR and Molecular Docking Study for Identification of Diverse Natural Products as Potent Pf ENR Inhibitors.
abstract: An in-house library of 200 molecules from natural plant products was designed in order to evaluate their binding to Plasmodium ACP enoyl reductase (ENR), a promising biological target for antimalarial chemotherapeutics. The binding site of PfENR was explored computationally and the molecules were docked using AutoDock. Furthermore, the top-ranked scaffolds from docking studies were also compared with known PfENR inhibitors using 3D-QSAR. To this effect, a 3D-QSAR model was derived from a set of experimentally established PfENR inhibitors, using Comparative Molecular Force Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The best optimum CoMFA model exhibited a leave-one-out correlation coefficient (q2) and a noncross- validated correlation coefficient (r2) of 0.630 and 0.911, respectively. The result of this cumulative approach proposed five structurally distinct natural products as potent PfENR inhibitors. This study may lay a stepping stone towards Functional oriented synthesis (FOS) of novel PfENR inhibitors in future.
authors.forename: Preeti
authors.initials: P
authors.lastname: Wadhwa
authors.forename: Debasmita
authors.initials: D
authors.lastname: Saha
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India. anujfcy@iitr.ernet.in.
authors.forename: Anuj
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001688:Biological Products; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)