Cytotoxicity and pro-apoptosis activity of synthetic 1,3-thiazole incorporated phthalimide derivatives on cancer cells.

OBJECTIVES

Cancer is the second important reason for death worldwide. In spite of advances in cancer treatment, however, survival of patients stays weak. Therefore, there is a critical need for advancement of new anticancer drugs. Regarding the hopeful biological activity of phthalimide derivatives, in this study, synthesis, cytotoxicity, and pro-apoptosis activity of eleven derivatives of thiazole bearing phthalimide structure were evaluated.

MATERIALS AND METHODS

First, target derivatives were synthesized. All synthesized compounds were characterized by spectroscopic methods. Cytotoxicity and pro-apoptosis activity of the synthesized compounds were evaluated in MDA-MB-468, PC-12, and MCF-7 cancer cell lines by MTT assay, caspase-3 activity, and TUNEL assay. Finally, expression of BAX, BCL-2, and FAS (as markers of apoptosis) was assessed by the RT-PCR procedure.

RESULTS

Among the eleven compounds, (IC = 0.2±0.01 µM) was found to be the most potent derivative against MCF-7 cells. Also, Compound and showed strong cytotoxic activity against MDA-MB-468 and PC-12 cells with IC value of 0.6±0.04 µM and 0.43±0.06 µM, respectively. DNA fragmentation and activity of caspase-3 data suggest that cytotoxic activity of the compounds on cancer cells might be related to apoptosis. Also, RT-PCR of apoptosis markers indicated that these compounds induce apoptosis through the intrinsic pathway.

CONCLUSION

Our findings suggest that chloro derivative () may be a promising agent for treatment of cancer cells by the targeted intrinsic pathway of apoptosis and could be used as a drug candidate for assessment in the treatment of cancer.