阿尔茨海默病蛋白质组取代基的QSBR摄动理论和雷沙吉兰噻吩等排物的理论研究多目标挖掘

Title:Multi-Target Mining of Alzheimer Disease Proteome with Hansch’s QSBR-Perturbation Theory and Experimental-Theoretic Study of New Thiophene Isosters of Rasagiline

Volume: 18 Issue: 5

关键词: 阿尔茨海默病、神经变性疾病、海马蛋白质组，雷沙吉兰衍生物，药物–目标结合，QSBR模型摄动理论。

摘要: Hansch’s model is a classic approach to Quantitative Structure-Binding Relationships (QSBR) problems in Pharmacology and Medicinal Chemistry. Hansch QSAR equations are used as input parameters of electronic structure and lipophilicity. In this work, we perform a review on Hansch’s analysis. We also developed a new type of PT-QSBR Hansch’s model based on Perturbation Theory (PT) and QSBR approach for a large number of drugs reported in CheMBL. The targets are proteins expressed by the Hippocampus region of the brain of Alzheimer Disease (AD) patients. The model predicted correctly 49312 out of 53783 negative perturbations (Specificity = 91.7%) and 16197 out of 21245 positive perturbations (Sensitivity = 76.2%) in training series. The model also predicted correctly 49312/53783 (91.7%) and 16197/21245 (76.2%) negative or positive perturbations in external validation series. We applied our model in theoretical-experimental studies of organic synthesis, pharmacological assay, and prediction of unmeasured results for a series of compounds similar to Rasagiline (compound of reference) with potential neuroprotection effect.

Cite this article as:

Multi-Target Mining of Alzheimer Disease Proteome with Hansch’s QSBR-Perturbation Theory and Experimental-Theoretic Study of New Thiophene Isosters of Rasagiline, Current Drug Targets 2017; 18 (5) . https://dx.doi.org/10.2174/1389450116666151102095243