Identification of natural products for the treatment of Alzheimer’s disease: 3D-similarity search

Glycogen synthase kinase 3 (GSK-3), one of the main tau kinases involved in a variety of cellular processes, has been evidenced as a promising target for Alzheimer’s disease (AD) treatment. In recent years, great efforts have been made to discover new molecules with an enhanced profile that inhibit GSK-3 and display efficacy in AD treatment. SAR502250, a new discover selective GSK3 inhibitor with AD therapeutic potential, represents a good alternative to future design specific inhibitors against this condition. SAR502250 was used as a query in a 3D similarity search on the SPECS database to select new natural compounds as possible GSK-3 inhibitors. According to ShapeTanimoto, TanimotoCombo, and ComboScore matrics, the first 10 SPECS natural compounds were selected and structurally analyzed. The ADMETox, physicochemical parameters, and toxicity related risks profiles of the selected natural compounds were also investigated. The 3D-similarity results in conjunction with pharmaceutical profiles revealed the potential use of natural compounds as GSK-3 inhibitors for Alzheimer's disease therapy.