7. Medicinal Chemistry

(M. Abid, S. Landge, S. Mhadgut, S. Jemaal, N. Haughey, L. Teixeira, O. De Paolis, C. Walker, A. Schmidt, C. Jackson)

Misfolded, amyloid-like protein deposits in cells and tissues are commonly associated with numerous human diseases, including Alzheimer’s disease (AD), prion diseases (e.g. vCreutzfeldt-Jakob disease), Parkinson’s disease, Type-II diabetes etc. representing tremendous medical, social and financial problems. The Alzheimer’s disease involves the formation of extracellular amyloid-beta (Abeta) peptide into fibrillar deposits known as amyloid plaques (senile plaques). These fibrils (polymeric aggregates) or soluble oligomeric intermediates of Abeta peptide (or both) are associated with pathology. Accordingly, the inhibition of both seeding and fibril growing process in Abeta self-assembly is a promising therapeutic strategy.
The goal of our work is to design and synthesize a new class of antifibrillogenic compounds. The inhibitors have been synthesized by our recently developed catalytic process. The effect of inhibitors on fibrillogenesis are tested in vitro by thioflavin-T fluorescence spectroscopy, Congo Red binding and high resolution transmission electron microscopy. Currently, a quantitative structure-activity relationship (QSAR) study of the inhibitors is undergoing.

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