Sulfonamides as multifunctional agents for Alzheimer's disease

被引：80

作者：

Bag, Seema ^{[1
]}

Tulsan, Rekha ^{[1
]}

Sood, Abha ^{[1
]}

Cho, Hyejin ^{[1
]}

Redjeb, Hana ^{[1
]}

Zhou, Weihong ^{[1
]}

LeVine, Harry, III ^{[2
,3
]}

Toeroek, Bela ^{[1
]}

Toeroek, Marianna ^{[1
]}

机构：

[1] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA

[2] Univ Kentucky, Dept Mol & Cellular Biochem, Chandler Sch Med, Lexington, KY 40536 USA

[3] Univ Kentucky, Ctr Aging, Lexington, KY 40536 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 03期

关键词：

Alzheimer's disease; Amyloid-beta; Cholinesterase inhibition; Antioxidant; Sulfonamides; BETA-AMYLOID AGGREGATION; ORGANOFLUORINE INHIBITORS; BIOLOGICAL-ACTIVITY; OXIDATIVE STRESS; FIBRIL FORMATION; THIOFLAVINE-T; ACETYLCHOLINESTERASE; PEPTIDE; DESIGN; OLIGOMERIZATION;

D O I：

10.1016/j.bmcl.2014.12.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 Ab self-assembly (fibril and oligomer formation), in modulating cholinesterase (AChE, BuChE) activity, and scavenging free radicals. Several compounds exhibited promising Ab 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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：626 / 630

页数：5

共 61 条

[31] THIOFLAVINE-T INTERACTION WITH SYNTHETIC ALZHEIMERS-DISEASE BETA-AMYLOID PEPTIDES - DETECTION OF AMYLOID AGGREGATION IN SOLUTION [J].