Synthesis and Biological Evaluation of Novel Isoxazole-Amide Analogues as Anticancer and Antioxidant Agents.

Cancer now is one of the leading causes of mortality in the world. There has been a lot of effort to discover new anticarcinogenic agents that allow treatment with fewer side effects. A series of isoxazole-carboxamide derivatives (-) were synthesised and evaluated for their cytotoxic activity against breast (MCF-7), cervical (HeLa), and liver (Hep3B) cancer cell lines and their antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results showed that and were the most active compounds against Hep3B cells, with a half-maximal inhibitory concentration (IC) of around 23 g/ml; showed the highest activity against HeLa cells, with an IC 15.48 g/ml. However, had the lowest IC (39.80 g/ml) against MCF-7 cells. By contrast, compound g was inactive against all cancer cell lines, with IC values >400 g/ml. Both and reduced Hep3B secretion of alpha-fetoprotein (to 1829.33 ± 65.91 ng/ml and 1758.66 ± 54.04 ng/ml, respectively). Furthermore, in cell cycle analysis, and induced a delay in the G2/M phase of 18.07%, which is similar to the doxorubicin positive control. Moreover, and reduced the necrosis rate of Hep3B threefold and instead shifted the cells to apoptosis. Our results indicate that and have potent and promising anticancer activity. However, compound was the most active as antioxidant agent (IC = 7.8 ± 1.21 g/ml) compared with Trolox as a positive control (IC 2.75 g/ml).