الفهرس | Only 14 pages are availabe for public view |
Abstract Cancer is considered as a major health problem worldwide, where the death rate is increased especially in the developing countries. This promotes medicinal chemists to search for new anticancer agents that inhibit different targets leading to more efficacies and less side effects compared to the traditional agents. Aurones, (Z)-2-benzylidenebenzofuran-3(2H)-ones, have received much attention because of their interesting biological activities. They have proved to be promising bioactive compounds with a broad spectrum of activities including anticancer, antioxidant, antiparasitic and antibacterial activities. Aurones exhibited strong antiproliferative properties against cancer cells by acting on variable targets through different modes of action. So, the present investigation deals with the synthesis of series of aurones belonging to 6-methoxy-benzofuran-3-ones Va-f, VIIIa-g and IXa-g, in addition to furoaurone derivatives belonging to 4-methoxy-furano-benzofuran-3-ones XIIIa,b, XIVa-g and XVIIa-e, to explore their antitumor activities. The antitumor activity of sixteen new compounds selected by National Cancer Institute, USA was screened against 60 cell lines. The furoaurone derivative, XIVa was found to be the most active one exhibiting promising growth inhibition against leukemia K562 (GI%=70.33) and melanoma MDA-MB-435 cells (GI%=79.61) at concentration 10 oM. The cytotoxic mechanism of the most active compound XIVa was investigated by performing: cell cycle analysis, apoptotic assay, caspase-3 activation assay and cyclin dependant kinase 2 inhibition assays against leukemia K562 and melanoma MDA-MB-435 cell lines |