Title:Multi-Target Directed Ligands (MTDLs): Promising Coumarin Hybrids for Alzheimer’s Disease
Volume: 18
Issue: 10
关键词:
阿尔茨海默病，香豆素混合素，AChE, MAO-B，多奈哌齐，他克宁。
摘要: Alzheimer’s disease (AZD) is an age-associated neurodegenerative disorder and is one of
the common health issues around the globe. It is characterized by memory loss and a decline in other
cognitive domains, including executive function. The progression of AZD is associated with complex
events, and the exact pathogenesis is still unrevealed. Various mechanisms which are thought to be
associated with the initiation of AZD include a decreased concentration of acetylcholine (ACh), deposition
of amyloid-β (Aβ) peptide, dyshomeostasis of redox metal ions, and prolonged oxidative stress.
Due to the simultaneous progression of diverse pathogenetic pathways, no ideal therapeutic agent has
been developed to date. The drugs which are available against AZD provide only symptomatic benefits
and do not have disease-modifying activity. Therefore, in search of ideal therapeutic candidates, the
concept of molecular hybrids has been under keen investigation for the past few years. Hybrid molecules
are able to inhibit or activate or modify the physiology of more than one target simultaneously.
Coumarin scaffold have shown the excellent potential of ACh esterase inhibition, MAO-B inhibition,
and anti-Aβ aggregation. In the present review, we have focused on different reported coumarin hybrids
as multi-target-directed agents against AZD. These include hybrids of coumarin with carbazole,
benzofuran, dithiocarbamate, quinoline, pargyline, tacrine, N-benzyl pyridinium, donepezil, purine,
piperidine, morpholine, aminophenol, benzylamino, halophenylalkylamidic, thiazole, thiourea, hydroxypyridinone,
triazole, piperazine, chalcone, etc. Along with the therapeutic potentials of these hybrids,
important clinical investigations and the structure-activity relationship have also been discussed
in this compilation.
