Screening of inhibitors of Taenia solium glycogen synthase Kinase-3β

Abstract

Glycogen synthase kinase-3β (GSK-3β) has been found to be a potential target for the effective treatment of diseases such as type 2 diabetes, Alzheimer's disease, and schizophrenia. GSK-3β has also been suggested as a target for the treatment of protozoan parasitic infections such as those caused by Leishmania spp., Plasmodium falciparum, and Trypanosoma brucei. In this study, we determined the sequence of GSK-3β from T. solium (TsGSK-3β), which encodes 434 amino acid residues, as it could be a potential drug target. We modeled the TsGSK-3β tertiary structure by applying the crystal structure of the HsGSK-3β protein (PDB ID: 1UV5) as the template. Fourteen inhibitors of TsGSK-3β were screened by structure-based molecule docking. Recombinant TsGSK-3β protein was expressed and purified. We obtained 14 pharmaceutical compounds and performed surface plasmon resonance imaging to determine their binding affinities to TsGSK-3β and HsGSK-3β. Three compounds were identified to be potential novel inhibitors, as they showed significant interaction with TsGSK-3β but no binding to HsGSK-3β. Our study provides useful information for finding innovative drugs for treatment of T. solium infections.