Multi-Targeting Tacrine Conjugates with Cholinesterase and Amyloid-Beta Inhibitory Activities: New Anti-Alzheimer's Agents

Chemistry & Biodiversity
Asha HiremathadRangappa S Keri

Abstract

Alzheimer's disease (AD) is a severe age dependent and chronic problem with no cure so far. The available treatments are temporary, acting over short period of time. The main pathological hallmark of the disease includes cholinergic dysfunction, oxidative stress, accumulation of Aβ fibrils and tau tangles. In context with the multi-factorial nature of this disease, two different series of molecules were developed to hit the multifactorial disease targets. Mainly, the molecules were designed to inhibit the AChE and aggregation of Aβ, and also oxidative damage. Two novel series of TAC-fenbufen/menbutone conjugated molecules were designed, synthesized and bio-assayed. All compounds showed inhibition capacity towards AChE, Aβ aggregation and moderate to good radical scavenging capacity. Particularly, five TAC-menbutone molecules showed improved AChE and Aβ aggregation inhibition capacity compared to TAC-fenbufen conjugated molecules. Overall, these novel series of molecules may be potential drug lead molecules in the treatment of AD.

References

Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Jun 25, 2005·Current Alzheimer Research·Zhen Yan, Jian Feng
Oct 14, 2006·Journal of Neural Transmission·R Schliebs, T Arendt
Oct 17, 2007·Chembiochem : a European Journal of Chemical Biology·Manuela BartoliniVincenza Andrisano
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ashley I Bush, Rudolph E Tanzi
Mar 31, 2009·Angewandte Chemie·Roland Jakob-Roetne, Helmut Jacobsen
Nov 12, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Jaroslav SebestíkM Amélia Santos
Sep 26, 2013·Current Medicinal Chemistry·Miroslav Pohanka
Jul 16, 2014·Alzheimer's Research & Therapy·Jeffrey L CummingsKate Zhong
Feb 22, 2018·European Journal of Medicinal Chemistry·Asha HiremathadM Amélia Santos

Related Concepts

Acetylcholinesterase
Alzheimer's Disease
Antineoplastic Agents
Oxidation
Problem
Tacrine
Fenbufen
Menbutone
Amyloid beta-Peptides
Tau Proteins

Related Feeds

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.