Citation: KANG Cong-Min, ZHAO Xu-Hao, WANG Xin-Yu, CHENG Jia-Gao, LÜ Ying-Tao. QSAR and Molecular Docking on Five-Membered Heterocyclopyrimidines as Thymidylate Synthase Inhibitors[J]. Acta Physico-Chimica Sinica, ;2013, 29(02): 431-438. doi: 10.3866/PKU.WHXB201211151 shu

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

  • Received Date: 27 August 2012
    Available Online: 15 November 2012

    Fund Project: 国家自然科学基金(21072111, 21172070, 21272131) (21072111, 21172070, 21272131)山东省自然科学基金(ZR2011BM015)资助项目 (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 od 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.

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