Design and synthesis of thienopyridines as novel templates for acetylcholinesterase inhibitors

Badran, Mohga M.; Hakeem, Maha Abdel; Abuel‐Maaty, Suzan M.; El‐Malah, Afaf; Salam, Rania M. Abdel

doi:10.1007/s00044-012-0403-5

Cited by 5 publications

(1 citation statement)

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“…The other analog 8b, with longer alkyl spacer and smaller size of tricyclic ring compared to 8a, was stronger AChEI (IC 50 = 3.65 nM) than tacrine (IC 50 = 5.46 nM) with 4685 times selectivity towards AChE over BChE (IC 50 = 17100 nM) [42]. The analogs 9, 10 (Figure 4) having thienopyridine joined with phthalimide and lipoic acid moieties respectively through a linker, showed 56% and 57% AChE enzyme inhibition respectively at 10mg/kg oral dose in adult male albino Wister rats similar to tacrine (55% AChE inhibition) [43]. A series of tacrine-phenyl-benzothiazole hybrids (11, 12 of Figure 5) were derived by connecting tacrine with benzothiazole moiety through an alkyl/amide spacer [44].…”

Section: Tacrine Analogsmentioning

confidence: 94%

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Saxena¹

2019

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Alzheimer's Disease (AD) is characterized by the loss of memory and learning ability in elderly patients affecting large population worldwide. The enzyme Acetylcholinesterase (AChE), (E.C.3.1.1.7) plays a major role in the hydrolysis of the released neurotransmitter acetylcholine. Most of the clinically used drugs to treat AD are Acetylcholinesterase Inhibitors (AChEIs). These drugs can provide symptomatic benefits only and suffer with loss of therapeutic potential with time. Therefore, there is an urgent need of novel cholinesterase inhibitors with wider therapeutic window for the treatment of AD. The strategies targeting the AChE enzyme along with other target(s) like Butyrylcholinesterase (BChE), amyloid-β (Aβ), β-secretase-1 (BACE), metals (Cu 2+ , Zn 2+ , or Fe 2+), antioxidant properties and free radical scavenging capacity have been mainly focused in the last five years. A number of hybrid molecules incorporating sub-structures with the desired well-established pharmacological profile into a single scaffold have been investigated. The main sub structures used in developing these molecules are derived from diverse chemical classes such as acridine, quinoline, carbamates, huperzine and other heterocyclic analogs. It has been followed by optimization of activity through structural modifications of the prototype molecules for developing the Structure Activity Relationship (SAR). This has led to the development of novel molecules with desired AChE inhibitory activity along with other desirable pharmacological properties. This review summarizes the current therapeutic strategies for the development of these AChEI in the last seven years.

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Section: Tacrine Analogsmentioning

confidence: 94%