title: 3D QSAR and docking study of flavone derivatives as potent inhibitors of influenza H1N1 virus neuraminidase.
abstract: Although several flavonoids have been reported to exert inhibitory effects on influenza H1N1 neuraminidase (NA), little is known about the structure-activity relationship and binding mode. Three dimensional QSAR (quantitative structure-activity relationship) and molecular docking approaches were applied to explore the structural requisites of flavone derivatives for NA inhibitory activity. A meaningful QSAR model with R(2) of 0.5968, Q(2) of 0.6457, and Pearson-R value of 0.8679, was constructed. From the QSAR model, it could be seen how 6-OH, 3'-OH, 4'-OH, and 8-position substituent affect the NA inhibitory activity. Molecular docking study between the most active compound and NA suggested that hydrogen bonds, hydrophobic and electrostatic interactions were closely related to NA inhibitory activity, 5-OH and 7-OH may be essential for this activity. The results provide a set of useful guidelines for the rational design of novel NA inhibitors.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China. gaoli@imm.ac.cn
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Mian
authors.initials: M
authors.lastname: Zu
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Liu
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D058990:Molecular Targeted Therapy; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D055672:Static Electricity
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D047309:Flavones; D008024:Ligands; D009439:Neuraminidase