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

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 ( I C 50 = 7.8 ± 1.21 μ g / ml ) compared with Trolox as a positive control (IC50 2.75 μg/ml).

Anticancer, Free Radicals, and Digestive Enzyme Inhibitory Activities of Rubus sanctus Schreb Root Four Solvent Fractions

“…To ensure that only DNA was stained, the treatment of cells with ribonuclease (50 μl of 100 μg/ml RNase) was done. en, cells were stained with 5 μl of 50 μg propidium iodide/100 ml and were analyzed using the flow cytometer (Becton-Dickinson LSR II, Immunofluorometry systems, Mountain View, CA) [29].…”

Preclinical Study of Immunological Isoxazole Derivatives as a Potential Support for Melanoma Chemotherapy

“…The isoxazole carboxamide derivatives were also assessed for their cytotoxic activity on breast (MCF-7) and liver (Hep3B) cancer cell lines, as well as on the cervix (HeLa). Only two compounds from this series showed promising anticancer activity, delaying the G2/M phase by 18.07% [22].…”

“…Chemotherapy is widely used, especially against inoperable tumors, as a basic therapy or as an adjunct treatment before and/or after subsequent treatment. However, the use of chemotherapy is limited because it has a poor efficacy; minimal target cell selectivity; and undesirable side effects, such as alopecia, nausea, and vomiting [22]. It is very important to search for new components of oncological therapy that will ensure the greater effectiveness of the therapy and, at the same time, will be free from troublesome side effects reducing the quality of life of an oncological patient.…”

Design, Synthesis, In Silico and In Vitro Studies of New Immunomodulatory Anticancer Nicotinamide Derivatives Targeting VEGFR-2

“…Accordingly, nicotinamidemoiety was utilized as a head in the synthesized compounds to maintain the essential H-bonding interaction at the hinge region. In addition, it was reported that amide moiety may exert an anticancer effect [33]. With respect to the linker segment, it is usually 3-5 bond lengths [34].…”