Design,Synthesis And Anti-Alzheimer Activity Evaluation Of α-Mangostin Analogues

Alzheimer’s Disease (AD) is a progressive, degenerative disorder of the central nervous system, characterized with continuous decline in memory and cognitive impairment. AD is the most common form of dementia among the olders. AD’s neurodegeneration is associated with the loss of the forebrain and the decreased level of acetylchoiline. One available method for AD’s treatment is to recover the level of acetylcholine or enhance the cholinergic transmission via inhibiting acetylcholinesterase.α-Mangostin, a xanthone derived from the pericap of G. mangostana, has exhibited a variety of biological and pharmacological activities.Furthermore, a-Mangostin has the similar structural feature to tacrine. In the first part, the initial substrate a-mangostin was converted into the cyclized compounds A-MG, B-MG, then, the 9-OH hydroxy site was substituted different isocyanates to afford 24 novel carbamates, which were qualitatively investigated by 1H-NMR,13C-NMR and MS.In the second part, those a-mangostin derivatives were evaluated for their anticholinesterase activities by modified spectrophotometry with galanthamine as the positive control. MG15, MG16, MG20 and MG24 displayed significantly twofold activity in anticholinesterase c ompared to a-mangostin. The neuroprotective effects of MG15, MG1 6, MG20 and MG24 were investigated in PC 12 cell model which w ere injured by H2O2. The result showed the viability of PC 12 cells a 11 could remarkably increased if pretreated with MG20 with different concentrations. The disscussion in the research could be a beneficial clue for further optimization and development of AD’s therapy.