Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line.
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| Abstract |
Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show a potent inhibitory activity of cell proliferation and cell cycle arrest at G2/M phase. Compounds 4c, 5e and 7c exhibit low to moderate β-tubulin polymerization inhibition percentage. Meanwhile, compound 6c displayed excellent β-tubulin percentage of polymerization inhibition equivalent to that exhibited by podo. In addition, compounds 4c, 5e and 7c show strong topoisomerase (topo) II inhibitory activity in nano-molar concentration, compared to known topo inhibitor as etoposide. Finally, apoptotic inducing activity over MCF-7 of compounds 4c, 5e, 6c and 7c is due to up-regulation of p53, increased Bax/Bcl-2 ratio and caspase3/7 levels 2-fold higher than podo.
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| Authors | Islam Zaki, Mohammed K Abdelhameid, Ibrahim M El-Deen, Abdel Hady A Abdel Wahab, Abeer M Ashmawy, Khaled O Mohamed |
| Journal | European journal of medicinal chemistry (Eur J Med Chem) Vol. 156 Pg. 563-579 (Aug 05 2018) ISSN: 1768-3254 [Electronic] France |
| PMID | 30025350 (Publication Type: Journal Article) |
| Copyright | Published by Elsevier Masson SAS. |
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