Wong Kai Y, Mercader Andrew G, Saavedra Laura M, Honarparvar Bahareh, Romanelli Gustavo P, Duchowicz Pablo R
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag, 113 y 64, Sucursal 4, C,C, 16, La Plata, 1900, Argentina.
J Biomed Sci. 2014 Sep 20;21(1):84. doi: 10.1186/s12929-014-0084-0.
The evaluation of the clinical effects of Tacrine has shown efficacy in delaying the deterioration of the symptoms of Alzheimer's disease, while confirming the adverse events consisting mainly in the elevated liver transaminase levels. The study of tacrine analogs presents a continuous interest, and for this reason we establish Quantitative Structure-Activity Relationships on their Acetylcholinesterase inhibitory activity.
Ten groups of new developed Tacrine-related inhibitors are explored, which have been experimentally measured in different biochemical conditions and AChE sources. The number of included descriptors in the structure-activity relationship is characterized by 'Rule of Thumb'. The 1502 applied molecular descriptors could provide the best linear models for the selected Alzheimer's data base and the best QSAR model is reported for the considered data sets.
The QSAR models developed in this work have a satisfactory predictive ability, and are obtained by selecting the most representative molecular descriptors of the chemical structure, represented through more than a thousand of constitutional, topological, geometrical, quantum-mechanical and electronic descriptor types.
对他克林临床效果的评估表明，其在延缓阿尔茨海默病症状恶化方面具有疗效，同时证实了主要由肝转氨酶水平升高构成的不良事件。对他克林类似物的研究一直备受关注，因此我们基于其乙酰胆碱酯酶抑制活性建立定量构效关系。
探索了十组新开发的与他克林相关的抑制剂，它们已在不同生化条件和乙酰胆碱酯酶来源下进行了实验测定。构效关系中纳入描述符的数量以“经验法则”为特征。所应用的1502个分子描述符可为选定的阿尔茨海默病数据库提供最佳线性模型，并针对所考虑的数据集报告了最佳定量构效关系模型。
本研究中开发的定量构效关系模型具有令人满意的预测能力，是通过选择化学结构中最具代表性的分子描述符获得的，这些描述符通过一千多种组成、拓扑、几何、量子力学和电子描述符类型来表示。
