MOLECULAR BINDING PROFILE OF PROTOBERBERINE ALKALOIDS ON GLYCOGEN SYNTHASE KINASE 3β AS a DRUG CANDIDATE FOR ALZHEIMER’S DISEASES

Objective: Protoberberine alkaloids such as berberine, palmatine, jatrorrhizine, columbamine, magnoflorine were found to prevent a progressive neurodegenerative disorder as experimentally, the mechanisms of them are not absolutely clear. In this study, we have aimed to elucidate the binding and affect mechanism of these alkaloids on the GSK-3β. Material and Method: Glycogen Synthase Kinase 3β (GSK-3β) is a serine/threonine kinase which has essential roles in Alzheimer’s Diseases (AD) processes. AD shows neuropathological markers as tau hyperphosphorylation and accumulation of amyloid β (Aβ) proteins. Aβ proteins are generated from sequential cleavages of amyloid precursor protein (APP). Recent studies show that inhibition of GSK-3β causes to decrease in the cleavage of APP. Thus the accumulation of Aβ was prevented by this process. Due to the therapeutic benefit of the inhibition of GSK-3β it has been a favoured target for scientists. Alkaloids are secondary metabolites which are produced by a large variety of organisms as plants with diverse structures. To explain the binding and the effect mechanism of GSK-3β, molecular docking studies were applied on these natural products by using CDOCKER module of Discovery Studio 3.5 Client. Binding mechanism was identified by Hydrogen, π bindings between ligands and GSK-3β. Result and Discussion: It has established that some protoberberine alkaloids with attractive properties about inhibition of GSK-3β. The molecules exhibited <-7.0 kcal/mol binding affinity values. Best docked results were detected with magnoflorine. In contrast with the other protoberberine alkaloids, magnoflorine has a compact structure. It could be more effective on binding affinity to receptor due to this reason