Acta Phys. -Chim. Sin. ›› 2013, Vol. 29 ›› Issue (02): 431-438.doi: 10.3866/PKU.WHXB201211151

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

QSAR and Molecular Docking on Five-Membered Heterocyclopyrimidines as Thymidylate Synthase Inhibitors

KANG Cong-Min1, ZHAO Xu-Hao1, WANG Xin-Yu1, CHENG Jia-Gao2, LÜ Ying-Tao1   

  1. 1 College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, Shandong Province, P. R. China;
    2 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. China
  • Received:2012-08-27 Revised:2012-11-14 Published:2013-01-14
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21072111, 21172070, 21272131) and Shandong Provincial Natural Science Foundation, China (ZR2011BM015).


The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 38 five-membered heterocyclopyrimidine thymidylate synthase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q2) was 0.662, the non-cross-validated value (R2) was 0.921, and the external cross-validated value (Qext2) was 0.85. And with the CoMSIA model, the corresponding q2, R2, and Qext2 values were 0.672, 0.884, and 0.81, respectively. The mode of action obtained by molecular docking was in agreement with the 3D-QSAR results. The results revealed that both models have good predictive capability to guide the design and structural modification of homologic compounds. Furthermore, these results also establish a base level for further research and development of new thymidylate synthase inhibitors.

Key words: Five-membered heterocyclopyrimidine derivative, Three dimensional quantitative structure-activity relationship, Comparative molecular field analysis, Comparative molecular similarity indices analysis, Molecular docking


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