Acta Phys. -Chim. Sin. ›› 2007, Vol. 23 ›› Issue (07): 1059-1064.doi: 10.3866/PKU.WHXB20070718

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Flavonoids with Aldose Reductase Inhibiting Activity: PharmacophoreModeling and Implications forMechanism

LIU Hai-Bo; WANG Zhan-Li; QIAO Ying-Xin; ZHOU Jia-Ju   

  1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, P. R. China; Graduate University of the Chinese Academy of Sciences, Beijing 100049, P. R. China; Technology Center, Neo Trident Technology Ltd., Beijing 100080, P. R. China
  • Received:2007-01-10 Revised:2007-03-28 Published:2007-07-03
  • Contact: ZHOU Jia-Ju E-mail:jjzhou@home.ipe.ac.cn

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Abstract: A three-dimensional pharmacophore model was generated for aldose reductase (ALR2) inhibitors with flavonoid skeleton, using the software Catalyst. Specially customized features of hydrogen-bond acceptor and donor were used in this study, which perform better than the default features of Catalyst. The hypothesis model was scored based on the cost of the hypothesis from the null hypothesis. The final selected pharmacophore model had three features; one hydrogen bond acceptor and two donors. Six flavonoid compounds were used to dock into ALR2 active site, using InsightII/Affinity. Comparison between the pharmacophore model and the docking results suggested that the C7 and C4’ hydroxyls on the flavone skeleton were key functional groups influencing ALR2 inhibotory activity, and TYR48, VAL47, GLN49, HIS110, and TRP111 at the active site of ALR2 were the key residues for the binding.

Key words: Aldose reductase inhibitor, Flavonoids, Pharmacophore model

MSC2000: 

  • O641