Abstract
A novel series of fourteen substituted selenadiazoles has been synthesized and the compounds tested for their in vitro antiproliferative and cytotoxic activities. The tests were carried out against leukemia (CCRF‐CEM), colon (HT‐29), lung (HTB‐54), and breast (MCF‐7) cancer cells. In order to assess the selectivity of the compounds under investigation the assays were also carried out on two non‐tumoral lines – one mammary (184B5) and one bronchial epithelium (BEAS‐2B) cell line. Assay‐based antiproliferative activity studies revealed that seven derivatives (2a, 2c, 2e, 2f, 2g, 3a, and 3b) exhibited good activity against MCF‐7 cells: for instance, 2c and 2f inhibited cell growth with nanomolar GI~50~ values. Compound 2f had a better antitumoral profile than vinorelbine and paclitaxel, two drugs that are used as first‐line treatments in advanced, recurrent, and/or metastatic cancer. In the other cell lines the compounds showed moderate activity or were inactive – with the exception of 2a, which was also found to have antiproliferative activity. Modulation of the cell cycle and apoptotic effects of active compounds were further evaluated in MCF‐7 cells. Of these, 6‐bromo[1,2,5]selenadiazolo[3,4‐b]pyridine (2a) was the most active, with an apoptogenic effect 3.9 times higher than that of camptothecin, which was used as a positive control. Compound 2a also provoked cell cycle arrest with a significant decrease in the G~0~/G~1~ phase cell population and an increase in S and G~2~/M cells, thus suggesting mitotic arrest prior to metaphase.