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 ( I C 50 = 7.8 ± 1.21 μ g / ml ) compared with Trolox as a positive control (IC50 2.75 μg/ml).
Non-steroidal anti-inflammatory drugs are among the most used drugs. They are competitive inhibitors of cyclooxygenase (COX). Twelve novel compounds (aryl acetate and aryl acetic acid groups) were synthesized in this work in order to identify which one was the most potent and which group was most selective towards COX1 and COX2 by using an in vitro COX inhibition assay kit. The cytotoxicity was evaluated for these compounds utilizing MTS assay against cervical carcinoma cells line (HeLa). The synthesized compounds were identified using FTIR, HRMS, 1H-NMR, and 13C-NMR techniques. The results showed that the most potent compound against the COX1 enzyme was 4f with IC50 = 0.725 µM. The compound 3b showed potent activity against both COX1 and COX2 with IC50 = 1.12 and 1.3 µM, respectively, and its selectivity ratio (0.862) was found to be better than Ketoprofen (0.196). In contrast, compound 4d was the most selective with a COX1/COX2 ratio value of 1.809 in comparison with the Ketoprofen ratio. All compounds showed cytotoxic activity against the HeLa Cervical cancer cell line at a higher concentration ranges (0.219–1.94 mM), and the most cytotoxic compound was 3e with a CC50 value of 219 µM. This was tenfold more than its IC50 values of 2.36 and 2.73 µM against COX1 and COX2, respectively. In general, the synthesized library has moderate activity against both enzymes (i.e., COX1 and COX2) and ortho halogenated compounds were more potent than the meta ones.
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