CAJ | 학술논문

用比较分子场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)研究了38个五元杂环并嘧啶衍生物类胸苷酸合成酶抑制剂的三维定量构效关系(3D-QSAR),建立了相关预测模型. CoMFA和CoMSIA模型的交互验证相关系数q2分别为0.662和0.672、非交互验证相关系数R2分别为0.921和0.884、外部交互验证相关系数Q2ext分别为0.85和0.81.分子对接得到的结合模式与三维定量构效关系得到的结果一致.结果表明这两种模型都具有良好的预测能力,可应用于指导化合物的设计和结构修饰,为进一步设计新型胸苷酸合成酶抑制剂提供了理论依据.
용비교분자장분석법(CoMFA)화비교분자상사성지수분석법(CoMSIA)연구료38개오원잡배병밀정연생물류흉감산합성매억제제적삼유정량구효관계(3D-QSAR),건립료상관예측모형. CoMFA화CoMSIA모형적교호험증상관계수q2분별위0.662화0.672、비교호험증상관계수R2분별위0.921화0.884、외부교호험증상관계수Q2ext분별위0.85화0.81.분자대접득도적결합모식여삼유정량구효관계득도적결과일치.결과표명저량충모형도구유량호적예측능력,가응용우지도화합물적설계화결구수식,위진일보설계신형흉감산합성매억제제제공료이론의거.
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 (Q2ext) was 0.85. And with the CoMSIA model, the corresponding q2, R2, and Q2ext 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.