Exploring Quinoxalinone Derivatives as Promising Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for Cancer Therapy
Issued Date
2024-05-01
Resource Type
ISSN
01252526
Scopus ID
2-s2.0-85196797702
Journal Title
Chiang Mai Journal of Science
Volume
51
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Chiang Mai Journal of Science Vol.51 No.3 (2024)
Suggested Citation
Jiwacharoenchai N., Kiriwan D., Tabtimmai L., Seetaha S., Yotphan S., Suwattanasophon C., Choowongkomon K. Exploring Quinoxalinone Derivatives as Promising Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for Cancer Therapy. Chiang Mai Journal of Science Vol.51 No.3 (2024). doi:10.12982/CMJS.2024.049 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/99254
Title
Exploring Quinoxalinone Derivatives as Promising Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for Cancer Therapy
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Corresponding Author(s)
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Abstract
EGFR plays an extensive role in the signaling pathway such as proliferation, migration, invasion. However, the malfunctioning of the epidermal growth factor receptor (EGFR) is a crucial factor in cancer progression. The search for new kinase inhibitors is necessary due to the evolving nature of diseases and the emergence of resistant strains, prompting the need for novel compounds that can effectively target and inhibit specific kinases for therapeutic purposes. This study explores quinoxalinone derivatives, comprised of benzene and pyrazine aromatic rings, as novel potential EGFR kinase inhibitors for cancer therapy, fulfilling an essential need in targeted cancer treatments. We utilized molecular docking to examine 46 synthesized quinoxalinone derivatives for their interaction with the tyrosine kinase domain of EGFR. Fifteen compounds exhibited strong binding affinities. Notably, LS3c, MN333, and MN343 displayed significant inhibitory effects on A431 cells with half-maximum inhibitory concentration (IC50) values comparable to gefitinib, erlotinib, and afatinib in enzymatic kinase assays. Subsequent experiments revealed that LS3c and MN343 effectively inhibit EGFR-expressing cell lines with low hepatotoxicity. MN343, the most potent compound, was selected for molecular dynamic simulation to understand its interaction with the tyrosine kinase of EGFR. To investigate the interaction between MN343 and EGFR’s tyrosine kinase, MM-PBSA analysis identified key residues (L694, V702, L768, M769, and L820) crucial for interaction, highlighting the potential of MN343 as a clinical EGFR tyrosine kinase inhibitor. The need for discovering new kinase inhibitors arises from the dynamic nature of diseases and the appearance of resistant strains, emphasizing the requirement for innovative compounds capable of targeting and inhibiting specific kinases effectively for therapeutic applications.