Design, synthesis and in vitro antitumor activity of novel N-substituted-4-phenyl/benzylphthalazin-1-ones

European Journal of Medicinal Chemistry
Wagdy M EldehnaMohieldin M Youssef

Abstract

A novel series of N-substituted-4-phenylphthalazin-1-ones 14a-g bearing different anilines at the N-2 of phthalazin-1-one scaffold via acetyl-flexible linker was designed and synthesized for the development of potential anticancer agents. Compounds 19a-g were synthesized by insertion of methylene (CH2) bridge at C4-position of 14a-g to provide a flexibility for the phenyl group. The newly synthesized compounds 14a-g and 19a-g were evaluated for their anti-proliferative activity against three human tumor cell lines HepG2 hepatocellular carcinoma, HT-29 colon cancer and MCF-7 breast cancer. In particular, HepG2 and HT-29 cancer cell lines were more susceptible to the synthesized derivatives. Compound 19d (IC50 = 1.2 ± 0.09 μM) was found to be the most potent derivative against HepG2 as it was 2.9 times more active than doxorubicin (IC50 = 3.45 ± 0.54) and sorafenib (IC50 = 3.5 ± 1.04 μM). Compounds 14e, 14g, 19d and 19g with IC50 = (3.29 ± 0.45), (3.50 ± 0.846), (1.20 ± 0.09) and (3.52 ± 0.70) μM, respectively, were found to be active candidates against HepG2 cancer cells. Compounds 14e, 14g, 19d and 19g were able to induce apoptosis in HepG2, this was assured by; the significant increase in the percentage of annexin V-FITC-posit...Continue Reading

References

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Citations

Sep 29, 2015·European Journal of Medicinal Chemistry·Hatem A Abdel-AzizAbdullah Al-Dhfyan
Jun 14, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wagdy M EldehnaHatem A Abdel-Aziz
Nov 11, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiulian ChenYan Zhao
Dec 29, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Wagdy M EldehnaHatem A Abdel-Aziz
Jun 27, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Ahmed SabtLaila A Rashed
Oct 9, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Mohammed SedkiIbrahim M El-Sherbiny
Feb 7, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Wagdy M EldehnaHatem A Abdel-Aziz
Feb 3, 2016·Biological & Pharmaceutical Bulletin·Magda Ismail MarzoukKhaled Zakaria El-Baghdady
Jun 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed El-NaggarHatem A Abdel-Aziz
Aug 20, 2019·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Rasha Mohamed HassanMohamed Nabil Aboul-Enein

Related Concepts

Antineoplastic Agents
Cell Cycle
Dose-Response Relationship, Drug
Dye Exclusion Assays, Antitumor
Phthalazines
Structure-Activity Relationship
Tumor Cells, Cultured
Drug Modeling
Apoptosis, Intrinsic Pathway
HT29 Cells

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