Matos, Ana M.; Man, Teresa; Idrissi, Imane; Souza, Cleide C.; Mead, Emma; Dunbar, Charlotte; Wolak, Joanna; Oliveira, Maria C.; Evans, David; Grayson, James; Partridge, Benjamin; Garwood, Claire; Ning, Ke; Sharman, Gary; Chen, Beining; Rauter, Amelia P. published the artcile< Discovery of N-methylpiperazinyl flavones as a novel class of compounds with therapeutic potential against Alzheimer's disease: synthesis, binding affinity towards amyloid β oligomers (Aβo) and ability to disrupt Aβo-PrPC interactions>, Category: piperazines, the main research area is methylpiperazinyl flavone amyloid beta oligomer cellular prion protein.
With no currently available disease-modifying drugs, Alzheimer’s disease is the most common type of dementia affecting over 47 million people worldwide. In light of the most recent discoveries placing the cellular prion protein (PrPC) as a key player in amyloid βoligomer (Aβo)-induced neurodegeneration, we investigated whether the neuroprotective potential of nature-inspired flavonoids against Aβo-promoted toxicity would translate into the ability to disrupt PrPC-Aβo interactions. Hence, we synthesized a small library of flavones and studied their binding affinity towards Aβo by STD-NMR. C-glucosyl flavones exhibited improved binding affinity with morpholine, thiomorpholine or N-methylpiperazine rings attached to the flavone skeleton in ring B para position. Moreover, a N-methylpiperazinyl flavone displayed suitable physicochem. properties and optimal water solubility even without the sugar moiety, and a high interaction with Aβo involving the whole flavone core. Its C-glucosyl derivative, was, however, the best compound to inhibit PrPC-Aβo interactions in a dose-dependent manner, with 41% of inhibition capacity at 10μM. The potential of C-glucosyl flavones and their aglycons as protein-protein interaction inhibitors able to tackle PrPC-Aβo interactions is here presented for the first time, and supports this class of compounds as new prototypes for further development in the treatment of Alzheimer’s disease.
Pure and Applied Chemistry published new progress about Aglycons Role: BSU (Biological Study, Unclassified), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Category: piperazines.
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics