国际药学与生命科学研究与发展杂志

抽象的

New GSK-3? ATP-competitive inhibitors for the management of Alzheimer?s Disease: Design, Synthesis and Biological Evaluation

Reem K. Arafa

Alzheimer’s disease (AD) is a chronic neurodegenerative disease among the top most common age-related forms of dementia. Unfortunately, no current treatments are known to stop or reverse the progression of AD, though those in clinical use only temporarily improve symptoms. Consequently, the research society is in need of discovery of new biologically active molecules that can contribute to the control of AD. Hallmarks of AD include accumulation of amyloid-β (Aβ) protein and neurofibrillary tangles (NFTs). GSK-3β is a validated key player in the development of Aβ and NFTs palying  a crucial role in disease progression. Thus, it presents a valid target for new anti-AD drug’s development. This research work displays the results of design and discovery of new oxadiazole scaffold based molecules with ATP-competitive GSK-3β inhibitory activity (figure 1). Biological screening results of these new molecules show a promising activity profile for these new entities and pave the way for future development and optimization of those discovered leads. Molecular modeling studies were also performed to stand on postulated binding modes of these chemotypes to the ATP binding site of GSK-3β (Figure 2).