Identification of sulfonylated indolo[1,2-a] quinolines as EGFR tyrosine kinase inhibitors
3
Issued Date
2025-01-30
Resource Type
eISSN
20462069
Scopus ID
2-s2.0-85216918118
Journal Title
RSC Advances
Volume
15
Issue
5
Start Page
3139
End Page
3146
Rights Holder(s)
SCOPUS
Bibliographic Citation
RSC Advances Vol.15 No.5 (2025) , 3139-3146
Suggested Citation
Phetcharawetch J., Uppalabat T., Sawektreeratana N., Suwannapaporn P., Todsaporn D., Rungrotmongkol T., Muanprasat C., Kuhakarn C. Identification of sulfonylated indolo[1,2-a] quinolines as EGFR tyrosine kinase inhibitors. RSC Advances Vol.15 No.5 (2025) , 3139-3146. 3146. doi:10.1039/d4ra07467j Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/104229
Title
Identification of sulfonylated indolo[1,2-a] quinolines as EGFR tyrosine kinase inhibitors
Corresponding Author(s)
Other Contributor(s)
Abstract
Two series of indolo[1,2-a]quinolines (IQs), comprising six 6-trifluoromethylthio indolo[1,2-a]quinolines and nine 6-arenesulfonyl indolo[1,2-a]quinolines, were screened for their inhibitory activity against EGFR tyrosine kinase (EGFR-TK) using the ADP-Glo™ kinase assay. Among the 15 IQs screened, four compounds exhibited cytotoxic activity against a lung cancer cell line (A549) that was as potent as the known drug afatinib with lower cytotoxicity in Vero cells. In addition, while they displayed cytotoxic activity against a head and neck squamous cell carcinoma cell line (SCC cells), they were inactive against a colorectal cancer cell line (LS174T cells). Molecular dynamics (MD) simulations revealed that IQSO2R-I (IC50: 0.28 ± 0.05 mM) formed a stable complex with wild-type EGFR through hydrophohic interactions and hydrogen bonding with the K745 residue. Additionally, the compound complied with the extended rule of five. This class of compounds represents a novel class of EGFR-TK inhibitors, which may serve as a novel scaffold for the development of anticancer therapeutics targeting EGFR-TK.