Acta Phys. -Chim. Sin. ›› 2007, Vol. 23 ›› Issue (09): 1393-1398.doi: 10.3866/PKU.WHXB20070916

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Quantitative Structure-Activity Relationships of HIV-1 Integrase Inhibitors of DKAs

SHI Ya-Wei; LIU Zhen-Ming; JIN Hong-Wei; ZHANG Liang-Ren; ZHANG Li-He   

  1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, P. R. China
  • Received:2007-03-05 Revised:2007-05-25 Published:2007-09-06
  • Contact: ZHANG Liang-Ren

Abstract: The quantitative structure-activity relationships (QSAR) of a series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors of the derivatives of diketone acids (DKAs) were investigated using genetic function approximation (GFA) and moleculor field analysis (MFA) models and then validated by F-test and predictive-ability test. The r2pred of these two models reached 0.987 and 0.759, respectively, which demonstrated that the models had perfect predictive ability. Furthermore pharmocophore analysis was used to confirm the models and demonstrate the importance of hydrophobic interactions. Based on the above conclusions, three new molecules of DKAs with higher activity have been theoretically designed and are waiting for support from experiment. The findings in this research will give some guidance for designing novel effective HIV-1 integrase inhibitors.

Key words: Inhibitors of HIV-1 integrase, DKAs, GFA, MFA, Pharmocophore


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