New 1-phthalazinone Scaffold based Compounds: Design, Synthesis, Cytotoxicity and Protein Kinase Inhibition Activity

Title:New 1-phthalazinone Scaffold based Compounds: Design, Synthesis, Cytotoxicity and Protein Kinase Inhibition Activity

Volume: 18 Issue: 20

Author(s): Nehad E. Abo-elmagd, Riham F. George, Manal A. Ezzat and Reem K. Arafa*

Affiliation:

• University of Science and Technology, Zewail City of Science and Technology, Cairo, 12588,Egypt

Keywords: Cytotoxicity, EGFR, 1-Phthalazinone, VEGFR-2, xenograft, Cancer.

Abstract: Background & Method: A series of thirty-one new 1-phthalazinones was designed and synthesized based on the well-known VEGFR inhibitor vatalanib. The obtained phthalazinones were screened for their cytotoxic activity against DLD-1 and LoVo (colon), and Panc-1 and Paca-2 (pancreas) cancer cell lines using MTT assay. The tested compounds revealed exceptionally promising cytotoxic activity against LoVo cell lines with IC50 ranges 0.18-780 nM.

Conclusion: Finally, these compounds were also found to be dual inhibitors of VEGFR-2 and EGFR in the in vitro enzyme assay with higher potency against the former (IC50 = 0.023-0.41 nM).

Cite this article as:

Abo-elmagd E. Nehad , George F. Riham , Ezzat A. Manal and Arafa K. Reem *, New 1-phthalazinone Scaffold based Compounds: Design, Synthesis, Cytotoxicity and Protein Kinase Inhibition Activity, Mini-Reviews in Medicinal Chemistry 2018; 18 (20) . https://dx.doi.org/10.2174/1389557518666180903153254