Acta Phys. -Chim. Sin. ›› 2005, Vol. 21 ›› Issue (03): 333-337.doi: 10.3866/PKU.WHXB20050322

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3D-QSAR of Sulfonamide Hydroxamic Acid HDAC Inhibitors

LIU Bing; LU Ai-Jun; LIAO Chen-Zhong; LIU Hai-Bo; ZHOU Jia-Ju   

  1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080; Graduate School of the Chinese Academy of Sciences, Beijing 100039
  • Received:2004-08-18 Revised:2004-10-09 Published:2005-03-15
  • Contact: ZHOU Jia-Ju E-mail:jjzhou@home.ipe.ac.cn

Abstract: Histone deacetylase (HDAC) greatly affects the chromatin topology and gene expression, and HDAC can be a new strategy in human cancer or tumour therapy. Hydroxamic acid compounds are component of most of the HDAC inhibitors. Studies on quantitative structure-activity relationship (QSAR) with CoMFA for the bioactivities of a series of sulfonamide hydroxamic acid HDAC inhibitors were carried out successfully, and a good cross-validated correlation (q2=0.704) was obtained .The non-cross-validated partial least squares (PLS) model was also well built and analyzed by the prediction of the active data CoMFA steric, and electrostatic contours. The results show that steric field (0.697) plays a more important role in increasing bioactivity than that of electrostatic field (0.303), and the R5 position prefers a larger group, but the R1 position prefers a smaller group.

Key words: 3D-QSAR, CoMFA, Histone deacetylase, Sulfonamide hydroxamic acid,  Autodock