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

doi:10.1002/slct.201901487

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

Authors

Kamelia Amin

Ossama El‐Badry

Doaa Abdel Rahman

Dr Usama Ammar U.Ammar@napier.ac.uk
Lecturer

Abstract

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.

Citation

Amin, K., El‐Badry, O., Abdel Rahman, D., & Ammar, U. (2019). Synthesis and In Vitro Biological Evaluation of New Pyrido[2,3‐b]pyrazinone‐Based Cytotoxic Agents and Molecular Docking as BRAF Inhibitors. ChemistrySelect, 4(30), 8882-8885. https://doi.org/10.1002/slct.201901487

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
DOI	https://doi.org/10.1002/slct.201901487
Keywords	Cancer, Cytotoxicity, HCT 116, Pyrido[2,3-b]pyrazinone, V600EBRAF
Public URL	http://researchrepository.napier.ac.uk/Output/2974986

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