Virtual Screening, Molecular Docking, and DFT Studies of Some Thiazolidine-2,4-diones as Potential PIM-1 Kinase Inhibitors

摘要

In the present study, ZINC database has been used for virtual screening of thousand of compounds based on previously reported pharmacophore against PIM-1 kinase. These compounds were further screened by Glide docking methodologies such as high throughput virtual screening (HTVS), standard precision (SP) and extra precision (XP), against PIM-1 kinase (PDB ID: 4DTK). Eight top-ranked compounds ZINC22066185, ZINC05678245, ZINC16431468, ZINC05773728, ZINC36633741, ZINC16779084, ZINC19909862 and ZINC15056464, were selected by virtual screening and docking studies. These compounds were showed better binding affinities towards PIM-1 kinase by using amino acid residues such as LYS67, GLU171, ASP128, and ASP186. The top-ranked compounds were showed their predicted binding energies with PIM-1 kinase in the range of -9.06, -8.45, -8.96, -8.78, -8.63, -8.56,-8.56 and -8.30 kcal/mol, respectively. Various reference ligands of PDB ID: 4DTK, 3VBQ and 3VC4, were also taken for docking study on protein kinase (PDB ID: 4DTK) to find out the comparative Glide score of receptor ligand complexes. To confirm the inhibitors potencies, the orbital energies, such as HOMO and LUMO, of the hit compounds were calculated. The results of the study showed that ZINC22066185 and ZINC16779084, may be considered as prototype compounds for further development of potential PIM-1 inhibitors.