Graduate Student Campbell University Buies Creek, North Carolina, United States
Objective : To develop more effective drugs with extra antioxidative activity for the management of Alzheimer's Disease based on the Clioquinol and Ebselen hybrid lead compound.
Methods: Designed nine Clioquinol and Esbelen hybrid compound analogs with isothiocyanate and alpha-beta carbonyl side chains and virtually screened them for their binding affinity towards Keap1 (Kelch-like ECH-associated protein 1) to promote the disassociation of Keap1-Nrf2 (nuclear factor erythroid 2-p45 derived factor 2) complex to activate Nrf2 signaling.
Results: The addition of isothiocyanate and alpha-beta carbonyl motifs to Clioquinol and Ebselen hybrid structure increased the binding affinity of the newly designed compounds to Keap1 and could potentially promote the disassociation of Nrf2 from the Keap1-Nrf2 complex to activate Nrf2 signaling.
Conclusions: We found out from our study that adding an electrophilic chain to the Clioquinol and Esbelen hybrid compound would potentially introduce extra Nrf2-activating activity and add antioxidant activity to our lead compound to enhance its capacity in the management of Alzheimer’s Disease.
