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

A series of novel thiazolidine-2,4-dione derivatives 4a-x have been designed, synthesized and evaluated for potential anti-cancer activity. The anti-cancer activity of synthesized compounds 4a-x were evaluated against selected human cancer cell line of breast (MCF-7) using sulforhodamine B (SRB) method. Among the synthesized compounds, 4x having 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 compounds 4f, 4o and 4x having 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. (C) 2017 Elsevier B.V. All rights reserved.