Design, synthesis and molecular modeling studies of novel thiazolidine-2,4-dione derivatives as potential anti-cancer agents

摘要

AbstractA series of novel thiazolidine-2,4-dione derivatives4a-xhave been designed, synthesized and evaluated for potential anti-cancer activity. The anti-cancer activity of synthesized compounds4a-xwere evaluated against selected human cancer cell line of breast (MCF-7) using sulforhodamine B (SRB) method. Among the synthesized compounds,4xhaving 2-cyano phenyl group showed significant cytotoxic activity which is comparable to that of adriamycin as standard anti-cancer drug. The SAR study revealed that the substituted phenyl group on oxadiazole ring attached to thiazolidine-2,4-dione moiety showed significant growth inhibitory activity against MCF-7?cell line. The result of molecular modeling studies showed that compounds4f,4oand4xhaving similar structural alignment as crystal ligand of protein (PDB code:4DTK) and exhibited hydrogen bond interaction with amino acid residues LYS67, GLU171, ASP128 and ASP186 of PIM-1 kinase. The results of biological activity and docking study revealed that the presence of electron withdrawing group at 2 position of phenyl ring attached to oxadiazole of thiazolidine-2,4-dione scaffold is crucial for better anti-cancer activity.Graphical abstract