title: Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products.
abstract: NorA is a member of the Major Facilitator Superfamily (MFS) drug efflux pumps that have been shown to mediate antibiotic resistance in Staphylococcus aureus (SA). In this study, QSAR analysis, virtual screening and molecular docking were implemented in an effort to discover novel SA NorA efflux pump inhibitors. Originally, a set of 47 structurally diverse compounds compiled from the literature was used to develop linear QSAR models and another set of 15 different compounds were chosen for extra validation. The final model which was estimated by statistical values for the full data set (n = 45, Q(2) = 0.80, RMSE = 0.20) and for the external test set (n = 15, R(2) = 0.60, |res|max = 0.75, |res|min = 0.02) was applied on the collection of 182 flavonoides and the traditional Chinese medicine (TCM) database to screen for novel NorA inhibitors. Finally, 33 lead compounds that met the Lipinski's rules of five/three and had good predicted pIC50 values from in silico screening process were employed to analyze the binding ability by docking studies on NorA homology model in place of its unavailable crystal structures at two active sites, the central channel and the Walker B.
authors.forename: Khac-Minh
authors.initials: KM
authors.lastname: Thai
authors.forename: Trieu-Du
authors.initials: TD
authors.lastname: Ngo
authors.forename: Thien-Vy
authors.initials: TV
authors.lastname: Phan
authors.forename: Thanh-Dao
authors.initials: TD
authors.lastname: Tran
authors.forename: Ngoc-Vinh
authors.initials: NV
authors.lastname: Nguyen
authors.forename: Thien-Hai
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang, Dist. 1, Ho Chi Minh City, Viet Nam. thaikhacminh@gmail.com.
authors.forename: Minh-Tri
authors.initials: MT
authors.lastname: Le
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D062313:Databases, Pharmaceutical; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D016014:Linear Models; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005419:Flavonoids; D008024:Ligands; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus