Design, synthesis, and biological evaluation of phenyl-isoxazole-carboxamide derivatives as anticancer agents
Mohammed Hawash, Nidal Jaradat, Noor Bawwab, Kamilah Salem, Hadeel Arafat, Yousef Hajyousef, Tahrir Shtayeh, Shorooq Sobuh
Abstract
Abstract The present study aimed to design and synthesize a series of phenyl-isoxazole-carboxamide derivatives and investigate their antitumor and antioxidant activities. The in vitro cytotoxic evaluation was conducted using the MTS assay against four cancer cell lines: hepatocellular carcinoma (Hep3B and HepG2), cervical adenocarcinoma (HeLa), breast carcinoma (MCF-7), in addition to the normal cell line (Hek293T). Besides, the antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. All obtained compounds were found to have potent to moderate activities against Hep3B and MCF-7 cancer cells lines, except compound 2e . It was found that compound 2a has potent activity against HeLa and Hep3B cancer cell lines with IC 50 values of 0.91 and 8.02 µM, respectively. The IC 50 dose range of the tested compounds against Hep3B was 5.96–28.62 µM, except for 2e , compared with doxorubicin, which has an IC 50 value of 2.23 µM. Also, the IC 50 value range of the compounds against Hek293T was 112.78–266.66 µM, compared with doxorubicin, which has an IC 50 dose of 0.581 µM. The antioxidant activity of the synthesized compounds was weak, and compound 2d showed moderate activity against the DPPH enzyme with an IC 50 value of 138.50 µM in comparison with Trolox, which has an IC 50 dose of 37.23 µM.