Omid Tavallaei - Pharmaceutical Sciences Research Center, Health Institute, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
Milad Heidarian - Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
Marzieh Marzbany - Pharmaceutical Sciences Research Center, Health Institute, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
Alireza Aliabadi - Pharmaceutical Sciences Research Center, Health Institute, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Objective(s): 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-۴۶۸, PC-۱۲, and MCF-۷ cancer cell lines by MTT assay, caspase-۳ activity, and TUNEL assay. Finally, expression of BAX, BCL-۲, and FAS (as markers of apoptosis) was assessed by the RT-PCR procedure.Results: Among the eleven compounds, ۵b (IC۵۰ = ۰.۲±۰.۰۱ µM) was found to be the most potent derivative against MCF-۷ cells. Also, Compound ۵k and ۵g showed strong cytotoxic activity against MDA-MB-۴۶۸ and PC-۱۲ cells with IC۵۰ value of ۰.۶±۰.۰۴ µM and ۰.۴۳±۰.۰۶ µM, respectively.  DNA fragmentation and activity of caspase-۳ 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 para chloro derivative (۵c) 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 in vivo assessment in the treatment of cancer.

Apoptosis, Cancer cells, Cytotoxicity, Phthalimide, Thiazole