Synthesis of isatin-derived compounds and investigation of their antiproliferative and fluorescence properties in different cancer cell lines

Cancer continues to be a major global health problem, with incidence increasing worldwide. Breast cancer is one of the most common malignancies among women worldwide, increasing the need for more effective and selective treatment agents. In this context, isatin and its derivatives, which are widely used in cancer research and are found in the structure of many commercial anticancer drugs, and their conjugation with 4-bromo 1,8-naphthalimide were synthesized and characterized using spectroscopic FT-IR, 1H-NMR, 13C-NMR techniques. In vitro activity of the synthesized compounds against MCF-7 and MDA-MB-231 cell lines was evaluated by cytotoxicity and apoptosis assays. According to MTT results, especially compounds H and C showed strong cytotoxic effect on both two cell lines. In flow cytometry analysis, compounds H and M induced high levels of late apoptosis. Mitochondria and nucleus staining by confocal microscopy revealed a marked localization to the mitochondria. This accumulation towards mitochondria suggests that mitochondrial pathways are involved in the mechanism of apoptosis. Low toxicity was observed in HEK cells and these compounds were found to be selectively effective against cancer cells. In conclusion, compounds H and C have potent and selective anticancer potential and with its mitochondria-targeted effects, it has potential for further analysis as an anticancer agent. Key Words: Anticancer, cytotoxicity, fluorescence, isatin, naphthalimide