Simone
摘要: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 (q(2)) was 0.662,the non-cross-validated value (R-2) was 0.921,and the external cross-validated value (Q(ext)(2)) was 0.85.And with the CoMSIA model,the corresponding q(2),R-2,and Q(ext)(2) 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.
