Milelli Andrea, De Simone Angela, Ticchi Nicole, Chen Huan H, Betari Nibal, Andrisano Vincenza, Tumiatti Vincenzo
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini. Italy.
Curr Med Chem. 2017;24(32):3522-3546. doi: 10.2174/0929867324666170309123920.
The design of multifunctional agents represents one of the most active research field in medicinal chemistry. In particular, tacrine, a well known Acetylcholinesterase inhibitor, is one of the most used starting point to develop multifunctional ligands and hundreds of papers report about these new agents. This is the third review of a series concerning tacrinebased multifunctional ligands; in particular, in the present, we will summarize and discuss the most intriguing examples of tacrine-based multifunctional agents published since 2013 until 2016.
We analyzed the bibliographic databases for peer-reviewed publications concerning tacrine-based multifunctional agents possessing biological actions that go beyond the simple "cholinergic" blockage. These papers have been subdivided according to their biological activities. Since this is the third review of a series, we took into considerations only the papers appeared since 2013 until 2016.
In this review, we have analyzed more than 33 papers. All the reported compounds retain good inhibitory activity towards acetyl- and butyryl-cholinesterase. The other biological activities concern mostly inhibition of a) β-amyloid aggregation, b) β-secretase, c) monoamino oxidases, modulation of τ and ROS and metal chelation.
The analysis of the current literature reported in this review confirm the importance of tacrine as scaffold to develop multifunctional agents potentially usefull to contrast Alzheimer's disease. Furthermore, the compounds herein reported showed very intriguing biological activities that could be used as starting point to develop new compounds even more interesting and, hopefully, clinically usefull to contrast Alzheimer's Disease.
多功能药物的设计是药物化学中最活跃的研究领域之一。特别是，他克林作为一种著名的乙酰胆碱酯酶抑制剂，是开发多功能配体最常用的起始点之一，已有数百篇论文报道了这些新型药物。这是关于基于他克林的多功能配体系列综述的第三篇；具体而言，在本篇综述中，我们将总结和讨论2013年至2016年期间发表的基于他克林的多功能药物中最引人关注的实例。
我们分析了文献数据库中有关具有超越简单“胆碱能”阻断作用的基于他克林的多功能药物的同行评审出版物。这些论文已根据其生物活性进行了细分。由于这是该系列综述的第三篇，我们仅考虑了2013年至2016年期间发表的论文。
在本综述中，我们分析了33篇以上的论文。所有报道的化合物对乙酰胆碱酯酶和丁酰胆碱酯酶均保持良好的抑制活性。其他生物活性主要涉及对a)β-淀粉样蛋白聚集、b)β-分泌酶、c)单胺氧化酶的抑制，对τ和活性氧的调节以及金属螯合作用。
本综述中对当前文献的分析证实了他克林作为开发可能有助于对抗阿尔茨海默病的多功能药物的骨架的重要性。此外，本文报道的化合物显示出非常引人关注的生物活性，可作为开发更有趣且有望在临床上对抗阿尔茨海默病的新化合物的起点。
