Synthesis and evaluation of the cytotoxic activity of certain substituted benzopyrone derivatives / Marwa Samara Abbas Mohamed ; Supervised Fatma Abdelfattah Ragab , Enayat Ibrahim Aly , Heba Abdelrasheed Allam

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

Cancer continues to be one of the most serious life-threatening diseases. The serious development of drug resistant, particularly multidrug-resistant cancers make a tremendous request for novel anticancer drugs. Hybridization of coumarin moieties with different anticancer moieties is a promising strategy to reduces side effects, overcomes drug resistance and provides a valuable therapeutic intervention for treatment of cancer. Herein, twenty-five compounds were designed and synthesized by hybridizing coumarin with different pyrazole and pyrazoline moieties. The synthesized compounds were tested in the NCI against 60 human tumor cell lines according to the anticancer drug screening program where compounds VIIId, XId, XIIc, XVI and XVIIIa showed potent antitumor activity with low IC50 against different cell lines. Additionally, the most active compounds were tested for epidermal growth factor receptor EGFR, cyclo-oxygenase COX-2 and telomerase reverse transcriptase TERT enzymes inhibition assays. Cell cycle analysis and apoptosis of compounds VIIId, XId, XIIc and XVI have been accomplished. A molecular docking study for the most active compounds on the active site of the enzymes; EGFR (PDB: 1M17), COX-2 (PDB: 3LN1), TERT (PDB: 5CQG) was achieved to explore the interaction of these compounds with the active sites

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