zur Suche springenzur Navigation springenzum Inhalt springen

Sortieren nach: Erscheinungsjahr Typ der Publikation

Zeige Ergebnisse 1 bis 2 von 2.

Publikation

Shaaban, S.; Ashmawy, A. M.; Negm, A.; Wessjohann, L. A.; Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinoma Eur. J. Med. Chem. 179, 515-526, (2019) DOI: 10.1016/j.ejmech.2019.06.075

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.
Publikation

Shaaban, S.; Negm, A.; Ashmawy, A. M.; Ahmed, D. M.; Wessjohann, L. A.; Combinatorial synthesis, in silico, molecular and biochemical studies of tetrazole-derived organic selenides with increased selectivity against hepatocellular carcinoma Eur. J. Med. Chem. 122, 55-71, (2016) DOI: 10.1016/j.ejmech.2016.06.005

Novel tetrazole-based diselenides and selenoquinones were synthesized via azido-Ugi and sequential nucleophilic substitution (SN) strategy. Molecular docking study into mammalian TrxR1 was used to predict the anticancer potential of the newly synthesized compounds. The cytotoxic activity of the compounds was evaluated using hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cancer cells and compared with their cytotoxicity in normal fibroblast (WI-38) cells. The corresponding redox properties of the synthesized compounds were assessed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), glutathione peroxidase (GPx)-like activity and bleomycin dependent DNA damage. In general, diselenides showed preferential cytotoxicity to HepG2 compared to MCF-7 cells. These compounds exhibited also good GPx catalytic activity compared to ebselen (up to 5 fold). Selenoquinones 18, 21, 22 and 23 were selected to monitor the expression levels of caspase-8, Bcl-2 and Ki-67 molecular biomarkers. Interestingly, these compounds downregulated the Bcl-2 and Ki-67 expression levels and activated the expression of caspase-8 in HepG2 cells compared to untreated cells. These results indicate that some of the newly synthesized compounds possess anti-HepG2 activity.

Diese Seite wurde zuletzt am 11.02.2013 geändert.

IPB Mainnav Search