Hybrid Compounds for Alzheimers Disease

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As mentioned in the bivalent project, amyloid-beta, oxidative stress, biometal dyshomeostasis, and neuroinflammation have all been observed in Alzheimer's disease. One of our research interests focuses on the development of multifunctional ligands that can effectively target and reduce a variety of these factors simultaneously. To achieve this goal, we are exploring the beneficial effects of two common natural products: curcumin and melatonin. The protective effects of both of these compounds have been described in a wide range of diseases, in particular, neurodegenerative disorders. Specifically, curcumin has been shown to reduce amyloid-beta oligomerization, lower inflammatory cytokine production, and reduce oxidative stress. Melatonin has also been reported to have antioxidative abilities and decrease neuroinflammation. Using a hybrid molecule design approach, we have synthesized a curcumin-melatonin lead hybrid compound and a number of derivatives that have shown neuroprotection and antioxidative function in a cellular model of Alzheimer's disease. We are currently exploring the mechanisms of action of these novel hybrids and are working to develop more potent analogs with a strong synergistic activity profile as potential disease-modifying agents.‌