3-取代4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物抗肿瘤活性的定量构效关系研究

Study of the relationship between the structural indexes and antitumor activities of 3-substitutied-4-oxo-3 H-imidazo-[5,1-d][1,2,3,5] tetrazine-8-carboxylic acid and its derivatives

目的:研究3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物分子结构与抗肿瘤活性的关系。方法:采用量子化学和分子力学方法计算分子结构参数,利用Gram-Schmidt正交化法筛选参数,利用偏最小二乘法建立QSAR模型。结果:建立合理的3-取代-4-氧-3H-咪唑并[5,l-d][1,2,3,5]四嗪-8-羧酸衍生物抗肿瘤活性模型。结论:3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物抗肿瘤活性与分子油水分配系数LogP和8位取代基R_1上的非氢原子净电荷Q_1相关,研究结果可为同类抗肿瘤药物的分子设计提供参考。

Aim：to study the relationship between molecular indexes and anticancer activities of 3-substitutied-4-oxo-3 H-imidazo-[ 5,1- d ] [ 1,2,3,5 ] tetrazine-8-earboxylic acid and its derivatives. Method： the molecular indexes were calculated by quantum chemistry and molecular mechanics methods, which were selected on the Gram-Schmidt orthogonalization method. In addition, the QSAR model was established by PLS. Result：the QSAR model was set up successfully. Conclusion：the anticancer activities are relative to the LgP and the net charge Q1 of the substituent R1. The result may offer some references for the molecular design of the congener drugs.