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醛糖还原酶能促使体内的葡萄糖转化为山梨醇,与糖尿病并发症的发生和恶化有密切关系.研究显示黄酮类化合物具有较好的醛糖还原酶抑制能力.本文使用三维定量构效关系研究方法,包括比较分子场分析法和比较分子相似性指数分析法,建立76个黄酮类醛糖还原酶抑制剂的分子结构与生物活性之间的定量关系模型,为进一步进行该类抑制剂的活性与三维结构关系的研究提供重要依据.采用PLS分析法,得到了一个统计意义显著的构效关系模型,其交叉验证系数为0.666,非交叉验证相关系数为0.918,显示该模型具有较好的预测能力.该模型使用立体场、静电场、疏水场和氢键受体场,可以较好地解释抑制剂的活性与其结构的关系。此外,本文还使用“留九法”、Y-randomization和外部检验法等检验模型的稳定性和预测能力.本研究结果可为设计和开发活性更高的该类抑制剂提供理论参考.
Aldose reductase can promote glucose in the body into sorbitol, and diabetic complications are closely related to the occurrence and deterioration.Studies have shown that flavonoids have a good aldose reductase inhibitory capacity.In this paper, using three-dimensional quantitative structure-activity relationship Methods, including comparative molecular field analysis and comparative molecular similarity index analysis, established a quantitative relationship model between the molecular structure and bioactivity of 76 flavonoid aldose reductase inhibitors. In order to further carry out the activity of such inhibitors And the structure of the three-dimensional structure provide an important basis for the use of PLS analysis obtained a statistically significant structure-activity relationship model, the cross-validation coefficient of 0.666, non-cross-validation correlation coefficient of 0.918, shows that the model has a good prediction Ability.The model uses three-dimensional field, electrostatic field, hydrophobic field and hydrogen bond acceptor field, which can better explain the relationship between the activity of inhibitor and its structure. In addition, the stability and predictive ability of the proposed model are also tested by using the method of “leaving nine methods”, Y-randomization and external test, etc. The results of this study can provide theoretical reference for the design and development of more active inhibitors.