REQUIMTE / Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
Mini Rev Med Chem. 2012 Jun;12(6):583-91. doi: 10.2174/138955712800493744.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive dementia and loss of cognitive abilities. Until now, AD remains incurable. The principal biological target for AD therapy is acetylcholinesterase (AChE). Thus, the search for new drug candidates like AChE inhibitors constitutes an essential part for the discovery of more potent anti-AD agents. In general terms, rational drug design methodologies have played a decisive role. The present work is focused on the current state of the Ligand-Based Drug Design (LBDD) methods which have been applied to the elucidation of new molecular entities with high anti-AChE activity. Also, as a contribution to this field, we suggest a promising fragment-based approach for the search and prediction of new AChE inhibitors and for the fast and efficient extraction of substructural alerts which are responsible for the anti-AChE activity.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是进行性痴呆和认知能力丧失。到目前为止，AD 仍然无法治愈。AD 治疗的主要生物靶标是乙酰胆碱酯酶（AChE）。因此，寻找新的药物候选物，如 AChE 抑制剂，是发现更有效的抗 AD 药物的重要组成部分。一般来说，合理的药物设计方法学发挥了决定性的作用。目前的工作集中在基于配体的药物设计（LBDD）方法上，这些方法已被应用于阐明具有高抗 AChE 活性的新分子实体。此外，作为对该领域的贡献，我们提出了一种有前途的基于片段的方法，用于搜索和预测新的 AChE 抑制剂，并快速有效地提取负责抗 AChE 活性的亚结构警报。
