Skip to main content

Research Repository

Advanced Search

Synthesis and In Vitro Biological Evaluation of New Pyrido[2,3‐b]pyrazinone‐Based Cytotoxic Agents and Molecular Docking as BRAF Inhibitors

Amin, Kamelia; El‐Badry, Ossama; Abdel Rahman, Doaa; Ammar, Usama


Kamelia Amin

Ossama El‐Badry

Doaa Abdel Rahman


In this study, synthesis of new pyrido[2,3-b]pyrazinone derivatives were identified. The in vitro cytotoxic activity of synthesized compounds against human colon cancer cell line (HCT 116) and kinase assay (V600EBRAF) were investigated. The results revealed that compounds 4 b and 4 c (4-nitro and 4-methoxy benzylidene acid hydrazide substitution, respectively) were the most active compounds among the synthesized derivatives (IC50 12.120 and 13.103 μM, respectively). Moreover, they exhibited inhibitory activity against V600EBRAF (Inh % 79.23 and 81.33, respectively). In addition, the designed derivatives were subjected to be simulated with the active site of mutated BRAF kinase domain using a suitable molecular docking protocol. Docking results coincided with good activity of compound 4 c and showed high docking score with BRAF protein kinase domain −21.85171 kcal/mol better than native ligand. The results of this study consider pyridopyrazinone scaffold (with substituted phenyl ring through a spacer) a key nucleus for further molecular and structural optimization.

Journal Article Type Article
Acceptance Date Jul 31, 2019
Online Publication Date Aug 12, 2019
Publication Date Aug 14, 2019
Deposit Date Dec 11, 2022
Journal ChemistrySelect
Print ISSN 2365-6549
Electronic ISSN 2365-6549
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 4
Issue 30
Pages 8882-8885
Keywords Cancer, Cytotoxicity, HCT 116, Pyrido[2,3-b]pyrazinone, V600EBRAF
Public URL