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

• 作 者: GAOLi;ZUMian;WUSong;LIUAi-lin;DUGuan-hua;
• 机 构: Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beij
• 出 处: 中国药理学会第十一次全国学术会议
• 发表日期: 2011年期

　　OBJECTIVE To explore the structure activity relationship of a series of flavone derivatives with influenza H1N1 neuraminidase inhibitory activity, and to study the binding mode between the most active compound and neuraminidase.METHODS A series of flavone derivatives provided by National Center for pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences have been found to exert neuraminidase inhibitory activity.Three dimensional QSAR (quantitative structure-activity relationship) and molecular docking approaches were applied to explore the structural requisites of flavone derivatives for neuraminidase inhibitory activity.RESULTS A meaningful QSAR model with R2 of 0.5968, Q2 of 0.6457, and Pearson-R value of 0.8679, was constructed.It was concluded from the QSAR model that the 6-OH, 3-OH, 4-OH and 8-position substituent of flavone derivatives affected the neuraminidase inhibitory activity.Molecular docking results suggested that hydrogen bonds, hydrophobic and electrostatic interactions were closely related to neuraminidase inhibitory activity, 5-OH and 7-OH might be essential for this activity.CONCLUSION The results provide a set of useful guidelines for developing flavone derivatives as potent neuraminidase inhibitors in structure-based drug design and ligand-based drug design approach.