Bag Seema, Tulsan Rekha, Sood Abha, Cho Hyejin, Redjeb Hana, Zhou Weihong, LeVine Harry, Török Béla, Török Marianna
Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA, USA.
Department of Molecular and Cellular Biochemistry, Chandler School of Medicine, and Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Bioorg Med Chem Lett. 2015 Feb 1;25(3):626-30. doi: 10.1016/j.bmcl.2014.12.006. Epub 2014 Dec 9.
Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer's disease (AD). The potency of the compounds were assessed in the inhibition of Aβ self-assembly (fibril and oligomer formation), in modulating cholinesterase (AChE, BuChE) activity, and scavenging free radicals. Several compounds exhibited promising Aβ self-assembly and cholinesterase inhibition and in parallel, showed good free radical scavenging properties. The investigation of the scaffold described in this study resulted in the identification of three compounds (14, 19 and 26) as promising leads for the further design of multifunctional drug candidates for AD.
设计并合成了具有延伸线性结构的基于磺酰胺连接基的抑制剂，目的是开发针对阿尔茨海默病（AD）病理过程中多个环节的多功能药物。评估了这些化合物在抑制Aβ自组装（纤维和寡聚体形成）、调节胆碱酯酶（AChE、BuChE）活性以及清除自由基方面的效力。几种化合物表现出良好的Aβ自组装抑制和胆碱酯酶抑制作用，同时还具有良好的自由基清除性能。对本研究中所述支架的研究确定了三种化合物（14、19和26），作为进一步设计AD多功能候选药物的有前景的先导化合物。
