Synthesis, Structure, Bioactivity and Computational Avenue to Identify Structural Requirements of Novel 2-Imino-4-thiazolidinones as Anti-Tumour Agents

Cancer is a major public health problem in the United States and many other parts of the world. 4-thiazolidinone scaffold is an important group of heterocycles. A new series of 2-Imino-4-thiazolidinone derivatives were synthesized and tested for their cytotoxic activity against four cancer cell lines U937, THP-1, Colo205 and B16F10. From the results it was concluded that some of the compounds are found to be more active on U937 cell lines than the positive control anticancer drug, Etoposide. Our results indicate that all the test compounds (100%, IVa – s ) are active against U937 cells. In order to investigate further structural aspects, these compounds were subjected to molecular modeling studies. 2D-QSAR analysis (with robust, r 2 = 0.83, q 2 = 0.74 and pred_ r 2 = 0.80) suggests that the substitution of groups on tertiary carbon atom and groups containing lesser dipole moment on thiazolidinone core moiety could be beneficial for improving activity. Apart from this, 3D-QSAR analysis with 5 featured common pharmacophore hypothesis (AAAAR) also suggests the importance of hydrophobic substitution at R 3 , R 4 , R 5 positions on the phenyl ring connected to thiazolidinone core moiety for improving cytotoxic potency.