Virtual Screening for Novel Staphylococcus Aureus NorA Efflux Pump Inhibitors From Natural Products

Title:Virtual Screening for Novel Staphylococcus Aureus NorA Efflux Pump Inhibitors From Natural Products

Volume: 11 Issue: 2

Author(s): Khac-Minh Thai, Trieu-Du Ngo, Thien-Vy Phan, Thanh-Dao Tran, Ngoc-Vinh Nguyen, Thien-Hai Nguyen and Minh-Tri Le

Affiliation:

Keywords: Antibiotic resistance, docking, QSAR, virtual screening, NorA, staphylococcus aureus.

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, Q² = 0.80, RMSE = 0.20) and for the external test set (n = 15, R² = 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.

Cite this article as:

Thai Khac-Minh, Ngo Trieu-Du, Phan Thien-Vy, Tran Thanh-Dao, Nguyen Ngoc-Vinh, Nguyen Thien-Hai and Le Minh-Tri, Virtual Screening for Novel Staphylococcus Aureus NorA Efflux Pump Inhibitors From Natural Products, Medicinal Chemistry 2015; 11 (2) . https://dx.doi.org/10.2174/1573406410666140902110903