3D QSAR and docking study of flavone derivatives as potent inhibitors of influenza H1N1 virus neuraminidase

Li Gao; Mian Zu; Song Wu; Ai-Lin Liu; Guan-Hua Du

doi:10.1016/j.bmcl.2011.07.071

3D QSAR and docking study of flavone derivatives as potent inhibitors of influenza H1N1 virus neuraminidase

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5964-70. doi: 10.1016/j.bmcl.2011.07.071. Epub 2011 Jul 26.

Authors

Li Gao¹, Mian Zu, Song Wu, Ai-Lin Liu, Guan-Hua Du

Affiliation

¹ 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

PMID: 21843936
DOI: 10.1016/j.bmcl.2011.07.071

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / metabolism*
Antiviral Agents / pharmacology*
Computer Simulation
Drug Design*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism*
Enzyme Inhibitors / pharmacology*
Flavones / chemical synthesis
Flavones / chemistry
Flavones / metabolism*
Flavones / pharmacology*
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Influenza A Virus, H1N1 Subtype / drug effects
Influenza A Virus, H1N1 Subtype / enzymology*
Influenza A Virus, H1N1 Subtype / metabolism
Inhibitory Concentration 50
Ligands
Models, Molecular
Molecular Conformation
Molecular Targeted Therapy
Neuraminidase / antagonists & inhibitors*
Neuraminidase / chemistry
Neuraminidase / metabolism
Protein Binding
Quantitative Structure-Activity Relationship
Software*
Static Electricity

Substances

Antiviral Agents
Enzyme Inhibitors
Flavones
Ligands
Neuraminidase