Instituto Federal de Educação, Ciência e Tecnologia de Goiás, Câmpus Anápolis, Av. Pedro Ludovico, S/N - Residencial Reny Cury, Anápolis, GO, 75131-457, Brazil.
Grupo de Química Teórica e Estrutural de Anápolis (QTEA), Câmpus de Ciências Exatas e Tecnológicas, Universidade Estadual de Goiás, CP 459, Anápolis, GO, 75001-970, Brazil.
J Mol Model. 2019 Apr 11;25(5):116. doi: 10.1007/s00894-019-3993-8.
Alzheimer's disease is a widespread type of neurodegenerative dementia that mainly affects the elderly. Currently, this disease can only be treated palliatively. Existing drugs can only improve patients' symptoms. The search for new drugs that can effectively treat this disease is an important field of research in medicinal chemistry. Here we report a structure-activity relationship study of tacrine and some of its analogues in relation to their inhibitory activities against Alzheimer's disease. All of the molecular descriptors were calculated at the M062X/6-311++G(d,p) level of theory. Principal component analysis of the molecular descriptors showed that the compounds could be categorized into active and inactive compounds using just two descriptors: the HOMO and LUMO energies. These results should help us to explain the activities of tacrine derivatives and to model new tacrine analogues that are active against Alzheimer's disease. Graphical abstract PCA score plot for tacrine and its analogues.
阿尔茨海默病是一种广泛存在的神经退行性痴呆症，主要影响老年人。目前，这种疾病只能姑息治疗。现有的药物只能改善患者的症状。寻找能够有效治疗这种疾病的新药是药物化学的一个重要研究领域。在这里，我们报告了他克林及其一些类似物与它们对阿尔茨海默病的抑制活性的构效关系研究。所有的分子描述符都是在 M062X/6-311++G(d,p)理论水平上计算的。分子描述符的主成分分析表明，仅使用两个描述符（HOMO 和 LUMO 能量）就可以将化合物分为活性化合物和非活性化合物。这些结果应该有助于我们解释他克林衍生物的活性，并对新的针对阿尔茨海默病的他克林类似物进行建模。
