Abstract
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 (2a–2g) 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 2d and 2e were the most active compounds against Hep3B cells, with a half-maximal inhibitory concentration (IC50) of around 23 μg/ml; 2d showed the highest activity against HeLa cells, with an IC50 15.48 μg/ml. However, 2a had the lowest IC50 (39.80 μg/ml) against MCF-7 cells. By contrast, compound 2g was inactive against all cancer cell lines, with IC50 values >400 μg/ml. Both 2d and 2e 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, 2d and 2e induced a delay in the G2/M phase of 18.07%, which is similar to the doxorubicin positive control. Moreover, 2d and 2e reduced the necrosis rate of Hep3B threefold and instead shifted the cells to apoptosis. Our results indicate that 2d and 2e have potent and promising anticancer activity. However, compound 2a was the most active as antioxidant agent (IC50 = 7.8 ± 1.21 μg/ml) compared with Trolox as a positive control (IC50 2.75 μg/ml).
Highlights
Cancer is the leading cause of death throughout the world [1,2,3]
Compound 2g was inactive against all cancer cell lines, with IC50 values >400 μg/ml
The current project is aimed at synthesising novel isoxazole-carboxamide derivatives (2a–2g) with or without a methoxyphenyl moiety and at evaluating some of their biological activity such as antioxidant and anticancer activities on HeLa, MCF-7, HepG2, and HepB3 cancer cell lines
Summary
Cancer is the leading cause of death throughout the world [1,2,3]. 25% of the deaths in developing countries are due to cancer [4,5,6]. In the last few decades, researchers have synthesised many agents that have marked antioxidant activity, such as quinolinone-3-aminoamide [31], thienopyrimidine, thienopyrazole [34], and N-aryl-1,4-dihydropyridine derivatives [35]. These substances, like Trolox, a watersoluble vitamin E analogue, and rebamipide (Figure 2), exhibit effective antioxidant properties by scavenging unstable free radicals [31, 36, 37]. The current project is aimed at synthesising novel isoxazole-carboxamide derivatives (2a–2g) with or without a methoxyphenyl moiety and at evaluating some of their biological activity such as antioxidant and anticancer activities on HeLa, MCF-7, HepG2, and HepB3 cancer cell lines
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