Alzheimer's Disease is an irreversible neurodegenerative disease without a known cure that affects millions worldwide. It is estimated that every 3 seconds, someone is diagnosed with dementia; this calculates to be about 9.9 million new cases each year. Globally, of all the dementia cases, Alzheimer's Disease accounts for 60%-80%. In 2020, there were over 50 million dementia patients, which is expected to rise to 152 million by 2050 drastically. Every disease incurs a cost to the global economy, and Alzheimer's Disease currently costs USD 1 trillion every year, with this number expected to double by 2030. There are three famous hallmarks of Alzheimer's Disease; excessive extracellular deposition of amyloid-beta (Aβ) plaques, formation of neurofibrillary tangles due to modified tau proteins, and exacerbated the loss of synapses and neurons. Along with these hallmarks are the following hypotheses: amyloid hypothesis, tau hypothesis, cholinesterase hypothesis, and the metal ion hypothesis. The research aims to produce a series of multi-target directed chelates to address all the aforementioned hypotheses by enhancing the curcumin molecule with various poly-methoxy substituted aniline groups. Curcumin has been shown to inhibit tau aggregation and beta-secretase activity, bind to amyloid plaques and neurofibrillary tangles and reduce neurotic abnormalities. The poly-methoxy substituted anilines chosen were inspired by the biological activities of the methoxy pharmacophores on polymethoxy-flavones. The pharmacophores allowed the polymethoxy-flavones to display enhanced anti-inflammatory and beta-secretase inhibiting effects. Computational chemistry will be employed to predict the probability of success of each product, in tandem with <i>in vitro</i> analysis using assay kits. Structural analysis will be done via various techniques of NMR, Spectroscopy, and Thermogram.

Development of multi target directed chelates as a drug treatment for Alzheimer's disease

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.