利用分子力场分析法(comparative molecular field analysis,CoMFA)、比较分子相似性指数法(comparative molecular similarity indices analysis,CoMSIA)和分子对接方法对一系列喹唑啉类TNKS抑制剂进行三维定量构效关系研究。构建的CoM...利用分子力场分析法(comparative molecular field analysis,CoMFA)、比较分子相似性指数法(comparative molecular similarity indices analysis,CoMSIA)和分子对接方法对一系列喹唑啉类TNKS抑制剂进行三维定量构效关系研究。构建的CoMFA(q^(2)=0.578,r^(2)=0.998,r^(2)_(pred)=0.815)和CoMSIA(q^(2)=0.624,r^(2)=0.929,r^(2)_(pred)=0.747)模型具有良好的鲁棒性、预测能力和机制可解释能力。分子对接实验结果表明:Ser1221和Gly1185是影响这些抑制剂活性的主要氨基酸。研究对设计新型TNKS抑制剂具有参考意义。展开更多
应用比较分子力场分析(Comparative molecular force field analysis,CoMFA)方法研究了18种氟喹诺酮C-3噻唑酮衍生物对胰腺Capan-1细胞的体外抗增殖活性(p A).训练集中14个化合物用于建立预测模型,测试集6个化合物(含模板分子和新设计的...应用比较分子力场分析(Comparative molecular force field analysis,CoMFA)方法研究了18种氟喹诺酮C-3噻唑酮衍生物对胰腺Capan-1细胞的体外抗增殖活性(p A).训练集中14个化合物用于建立预测模型,测试集6个化合物(含模板分子和新设计的1个分子)作为模型验证.通过基于配体的原子契合的叠合方式,获得了训练集的统计显著模型.CoMFA模型使用3个主成分给出交叉验证系数(R 2 cv)值为0.436,非交叉验证系数(R 2)值为0.956,估计F值为72.217.结果显示,模型具有良好的稳健性与预测能力.基于CoMFA等高线图,揭示了该系列化合物抗增殖活性的一些关键结构因素.这些结果为理解其作用机制、设计具有高抗肿瘤活性的新型氟喹诺酮C-3噻唑酮类化合物提供有益的理论参考.展开更多
Aim and Method Comparative molecular field analysis (CoMFA), a threedimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a novelseries of C-3 substituted 4, 6-dichloioindole-2-carbo...Aim and Method Comparative molecular field analysis (CoMFA), a threedimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a novelseries of C-3 substituted 4, 6-dichloioindole-2-carboxylic acids to study the relationship betweentheir structure and the affinity for the glycine site of the NMDA receptor. Result Hie coefficientsof cross-validation q^2 and non cross-validation r^2 for the model established by the study are0.744 and 0.993, respectively, the value of variance ratio F is 261.343, and standard error estimate(SE) is 0.039. Conclusion These values indicate that the CoMFA model may have a good prediction forthe activity of C-3 substituted 4, 6-dichloroin-dole-2-carboxylic acids. As a consequence, thepredicted activity values of new designed compounds supports our conclusion from the model.展开更多
文摘组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)是近年来治疗癌症的重要靶向药物,其中羟氨酸类,苯甲酰胺类多种药物已进入临床试验阶段,但对于亲电酮类HDACi还有待于进一步研究,本研究应用比较分子力场分析法(comparative molecular field analysis,CoMFA),比较分子相似性指数法(compara-tive similarity indices analysis,CoMSIA)对29个亲电酮类HDAC抑制剂分子进行了定量构效关系分析,CoMFA模型的q2=0.668,r2=0.999;CoMSIA模型的q2=0.686,r2=0.995,所建模型预测能力较好。分子对接(sur-flex-dock)研究也进一步揭示出抑制剂分子与蛋白酶的作用模式,结合其作用模式比较合理地探讨了这类抑制剂的活性原因,为设计新型高效的亲电酮类HDACi提供了理论依据。
文摘利用分子力场分析法(comparative molecular field analysis,CoMFA)、比较分子相似性指数法(comparative molecular similarity indices analysis,CoMSIA)和分子对接方法对一系列喹唑啉类TNKS抑制剂进行三维定量构效关系研究。构建的CoMFA(q^(2)=0.578,r^(2)=0.998,r^(2)_(pred)=0.815)和CoMSIA(q^(2)=0.624,r^(2)=0.929,r^(2)_(pred)=0.747)模型具有良好的鲁棒性、预测能力和机制可解释能力。分子对接实验结果表明:Ser1221和Gly1185是影响这些抑制剂活性的主要氨基酸。研究对设计新型TNKS抑制剂具有参考意义。
文摘应用比较分子力场分析(Comparative molecular force field analysis,CoMFA)方法研究了18种氟喹诺酮C-3噻唑酮衍生物对胰腺Capan-1细胞的体外抗增殖活性(p A).训练集中14个化合物用于建立预测模型,测试集6个化合物(含模板分子和新设计的1个分子)作为模型验证.通过基于配体的原子契合的叠合方式,获得了训练集的统计显著模型.CoMFA模型使用3个主成分给出交叉验证系数(R 2 cv)值为0.436,非交叉验证系数(R 2)值为0.956,估计F值为72.217.结果显示,模型具有良好的稳健性与预测能力.基于CoMFA等高线图,揭示了该系列化合物抗增殖活性的一些关键结构因素.这些结果为理解其作用机制、设计具有高抗肿瘤活性的新型氟喹诺酮C-3噻唑酮类化合物提供有益的理论参考.
文摘Aim and Method Comparative molecular field analysis (CoMFA), a threedimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a novelseries of C-3 substituted 4, 6-dichloioindole-2-carboxylic acids to study the relationship betweentheir structure and the affinity for the glycine site of the NMDA receptor. Result Hie coefficientsof cross-validation q^2 and non cross-validation r^2 for the model established by the study are0.744 and 0.993, respectively, the value of variance ratio F is 261.343, and standard error estimate(SE) is 0.039. Conclusion These values indicate that the CoMFA model may have a good prediction forthe activity of C-3 substituted 4, 6-dichloroin-dole-2-carboxylic acids. As a consequence, thepredicted activity values of new designed compounds supports our conclusion from the model.
