Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinoma
- Eur J Med Chem. 2019 Oct 1:179:515-526. doi: 10.1016/j.ejmech.2019.06.075.
- 1. Chemistry Department, College of Science, King Faisal University, Al-Hofuf, Saudi Arabia; Organic Chemistry Division, Department of Chemistry, Faculty of Science, Mansoura University, Egypt. Electronic address: [email protected].
- 2. Cancer Biology Department, National Cancer Institute, Cairo University, Egypt.
- 3. BioChemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
- 4. Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Halle (Saale), Germany. Electronic address: [email protected].
Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good Anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.