基于CoMFA研究氟喹诺酮C-3噻唑酮衍生物抗胰腺癌活性  

Study on Anti-pancreatic Cancer Activity of Fluoroquinolone C-3 Thiazolone Derivatives Based on CoMFA

作　　者：冯长君[1] FENG Changjun(School of Materials and Chemical Engineering,Xuzhou Institute of Technology,Xuzhou 221018,China)

机构地区：[1]徐州工程学院材料与化学工程学院,江苏徐州221018

出　　处：《徐州工程学院学报（自然科学版）》2021年第3期8-12,共5页Journal of Xuzhou Institute of Technology(Natural Sciences Edition)

基　　金：国家自然科学基金项目(21075138);结构化学国家重点实验室开放基金项目(20160028)。

摘　　要：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.The comparative molecular force field analysis(CoMFA)method was used to study the antiproliferative activity(p A)of 18 fluoroquinolone C-3 thiazolone derivatives on pancreatic Capan-1 cells in vitro.The 14 compounds in the training set were used to establish a prediction model,and 6 compounds in the test set(including the template molecule and a newly designed molecule)were used as model verification.The statistically significant model of the training set was obtained through the superposition method based on the atomic fit of the ligand.The CoMFA model gave cross-validated coefficient(R 2 cv)value of 0.436 using 3 principal components,non-cross-validated(R 2)value of 0.956 with estimated F value of 72.217.The results showed that the model had strong stability and good predictability.Based on the contour map of CoMFA,some key structural factors of the anti-proliferative activity of this series of compounds are revealed.These results provide a useful theoretical reference for understanding its mechanism of action and designing new fluoroquinolone C-3 thiazolone compounds with high anti-tumor activity.

关 键 词：氟喹诺酮C-3噻唑酮衍生物 胰腺癌Capan-1细胞 抗肿瘤活性 比较分子力场分析法 分子设计 

分 类 号：R979.1[医药卫生—药品] R911[医药卫生—药学]