New pyrimidinone and fused pyrimidinone derivatives as potential anticancer chemotherapeutics.
A series of novel substituted pyrimidinones and fused pyrimidinones (compounds 3-18) were synthesized starting with oxiranylmethanone 2. The in vitro cytotoxicity against a human breast adenocarcinoma (MCF-7) cell line was investigated and most of the tested compounds showed potent cytotoxic activity against the MCF-7 cell line comparable to the activity of the commonly used anticancer drug cisplatin. Treatment of MCF-7 cells with increasing doses (2, 5, 10, and 20 µg/mL) of the tested compounds revealed that the activity of superoxide dismutase and the level of hydrogen peroxide were significantly increased, while the activities of catalase and glutathione peroxidase and the levels of reduced glutathione were significantly lowered compared with control MCF-7 cells. In general, derivatives 11 and 16 revealed the highest anticancer activity among the tested compounds.
National Research Center, Photochemistry Department, Dokki, Cairo, Egypt. aymnelzeny@yahoo.com
Aymn E
AE
Rashad
Ahmed H
AH
Shamroukh
Nabil M
NM
Yousif
Mowafia A
MA
Salama
Hatem S
HS
Ali
Mamdouh M
MM
Ali
Abeer E
AE
Mahmoud
Mahmoud
M
El-Shahat
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D061986:MCF-7 Cells; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009696:Nucleic Acids; D011744:Pyrimidinones; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase