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Design, synthesis, anticancer evaluation and molecular docking of new V600EBRAF inhibitors derived from pyridopyrazinone

Amin, Kamelia; El-Badry, Ossama; Abdel Rahman, Doaa; Ammar, Usama; Abdalla, Mohamed


Kamelia Amin

Ossama El-Badry

Doaa Abdel Rahman

Mohamed Abdalla


Design and synthesis of some new pyridopyrazinone derivatives as anti-proliferative agents is described. The cytotoxic activities of the synthesized compounds against melanoma cell line (LOXIMVI), ovarian cell line (OVCAR3), thyroid cell lines (CAL62, FTC133, BCPAP and ML1) and colon cell lines (HT29 and HCT116) were investigated. Results revealed that most compounds were active and compound 3d was the most active one. It exhibited promising activity against all tested cell lines. In addition, in vitro kinase assay against both WTBRAF and V600EBRAF was performed for all synthesized compounds. Furthermore, molecular docking of tested compounds was established with active site of V600EBRAF kinase domain. Results of kinase inhibition assay and molecular docking revealed that, compounds 1, 3d, e, h, i, 5d, e and 6b were potent inhibitors for V600EBRAF kinase enzyme involved in number of cancer types as melanoma, ovarian and thyroid cancer. The newly synthesized pyridopyrazinones substituted with different substituents at C-3 or fused with triazine heterocycle at C-3 and C-4 afforded potent V600EBRAF inhibitors and exhibited promising cytotoxic activities against different cancer types such as melanoma, ovarian, thyroid and colon cancer.

Journal Article Type Article
Acceptance Date Dec 5, 2015
Online Publication Date Mar 31, 2016
Publication Date 2016-03
Deposit Date Dec 11, 2022
Journal European Journal of Chemistry
Print ISSN 2153-2249
Publisher Eurochem Publishing
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
Pages 19-29
Keywords V600EBRAF; Melanoma; Colon cancer; Ovarian cancer; Thyroid cancer; Pyridopyrazinone
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