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

[ Vol. 18 , Issue. 20 ]

Author(s):

Nehad E. Abo-elmagd, Riham F. George, Manal A. Ezzat and Reem K. Arafa*   Pages 1759 - 1774 ( 16 )

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).

Keywords:

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

Affiliation:

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, University of Science and Technology, Zewail City of Science and Technology, Cairo, 12588

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