Identification of potential biological targets of oxindole scaffolds via in silico repositioning strategies

Background: Drug repurposing is an alternative strategy to traditional drug discovery that aims at predicting new uses for already existing drugs or clinical candidates. Drug has many advantages over development, such as reduced attrition rates, time and costs. This especially the case considering most investigated have been assessed their safety in trials. Repurposing campaigns can also be designed libraries of synthesized molecules different levels biological experimentation, from null in vitro vivo. Such extension “repurposing” concept expected provide significant identification novel drugs, synthetic accessibility desired compounds often one limiting factors pipeline. Methods: In this work, we performed a computational campaign on library previously oxindole-based compounds, order identify potential targets versatile scaffold. To aim, ligand-based approaches were firstly applied evaluate similarity degree compound library, with respect ligands extracted DrugBank, Protein Data Bank (PDB) ChEMBL databases. In particular, 2D fingerprint-based 3D shape-based profiles evaluated compared oxindole derivates. Results: The analyses predicted set candidate repurposing, some them emerging by consensus analyses. One identified targets, i.e., vascular endothelial growth factor receptor 2 (VEGFR-2) kinase, was further means docking calculations, followed testing candidate. Conclusions: While did not show potent inhibitory activity towards VEGFR-2, study highlighted several other possibilities therapeutically relevant may worth consideration repurposing.