Topomer comparative molecular field analysis (topomer CoMFA) is applied to the quantitative structure-activity relationship (QSAR) study of aminomethylenethiophene (AMT) derivatives as lysyl oxidase (LOX) inhibitors. A total of thirty-six AMT derivatives were selected to build the QSAR model. The established topomer CoMFA model has the non-cross-validated correlation coefficient (r2) of 0.912 and the leave-one-out correlation coefficient (q2) of 0.540, which is statistically significant. The theoretically predicted anti-LOX potency agrees well with the experimentally observed inhibitory activity, proving the reasonable predictive ability of the QSAR model. The effect of molecular field information on the LOX inhibition of substituted aminomethylenethiophene was discussed in detail. The structural modification of the aminomethylenethiophene scaffold was carried out, and novel AMT derivatives with theoretically decent LOX inhibition were proposed. The topomer CoMFA modeling could provide a quantitative perspective into the structure-activity relationship of AMT derivatives and potentially speed up the rational design of LOX inhibitors as antimetastatic agents for cancer therapy.

中文翻译：

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使用拓扑异构体比较分子场分析阐明氨基亚甲基噻吩衍生物作为赖氨酰氧化酶抑制剂的活性差异：对癌症治疗抗转移药物的合理设计的意义

拓扑异构体比较分子场分析 (topomer CoMFA) 应用于氨基亚甲基噻吩 (AMT) 衍生物作为赖氨酰氧化酶 (LOX) 抑制剂的定量构效关系 (QSAR) 研究。总共选择了 36 个 AMT 导数来构建 QSAR 模型。建立的拓扑异构体 CoMFA 模型的非交叉验证相关系数 (r2) 为 0.912，留一相关系数 (q2) 为 0.540，具有统计学意义。理论上预测的抗 LOX 效力与实验观察到的抑制活性非常吻合，证明了 QSAR 模型的合理预测能力。详细讨论了分子场信息对取代氨基亚甲基噻吩的LOX抑制作用的影响。对氨基亚甲基噻吩支架进行了结构修饰，并提出了具有理论上不错的 LOX 抑制作用的新型 AMT 衍生物。拓扑异构体 CoMFA 建模可以为 AMT 衍生物的构效关系提供定量视角，并有可能加快 LOX 抑制剂作为癌症治疗抗转移剂的合理设计。