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

European Journal of Medicinal Chemistry
Islam ZakiKhaled O Mohamed

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.

Citations

Sep 19, 2018·International Journal of Oncology·Zhong-Feng WangHai-Jun Li
Mar 21, 2019·Anti-cancer Agents in Medicinal Chemistry·Heba A E Mohamed, Hossa F Al-Shareef
Oct 1, 2019·Anti-cancer Agents in Medicinal Chemistry·Youstina W RizzkAmgad I M Khedr
Aug 7, 2020·Acta Crystallographica. Section C, Structural Chemistry·Konstantin L'vovich ObydennovTatiana Vladimirovna Glukhareva
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anthi PetrouAthina Geronikaki

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