【摘要】 氨肽酶N(aminopeptidase N,APN)在肿瘤细胞的生长、侵袭、转移和新血管生成等过程中发挥着关键作用,是抗肿瘤药物的重要靶点。本文应用比较分子力场分析法(Co MFA)对52个L-精氨酸类APN抑制剂进行了三维定量构效关系分析,得到的模型q2=0.532,最佳主成分数为4,回归相关系数r2=0.907,F=82.479,SEE=0.196,立体场和静电场对构效方程的贡献分别为64.3%和35.7%,结果表明模型有较好的预测能力。最后,用模型的系数等势图解释了分子结构与活性的关系,为进一步对L-精氨酸衍生物进行结构修饰提供依据。更多还原

【Abstract】 Aminopeptidase N(APN) plays a pivotal role in tumor growth, invasion, metastasis and angiogenesis. So it is useful to develop potential APN inhibitors as anticancer agents. In this paper, as a new class of APN inhibitors, 52 L-arginine derivatives were applied to 3D-quantitative structure activity relationship analysis by comparative molecular field analysis(Co MFA). The parameters of the Co MFA model are as follows: q2=0.532, n=4, r2=0.907, F=82.479, SEE=0.196. The contribution values of steric field and electrostatic field are 64.3% and 35.7%, respectively. The model showed good reliabilities and predictive abilities. Finally, the contour maps explained the relationship between the structures and activities, providing a theoretical foundation for further designing novel selective APN inhibitors.更多还原