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

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 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 (Q_ext²) was 0.85. And with the CoMSIA model, the corresponding q², R², and Q_ext² 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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