Discovery of new thieno[2,3-d]pyrimidines as EGFR tyrosine kinase inhibitors for cancer treatment

Background: EGFR has been considered a vital molecular target in cancer management. Aim: The discovery of new thieno[2,3-d]pyrimidine derivatives as EGFR tyrosine kinase inhibitors. Methods: Nine derivatives were designed, synthesized and subjected to in vitro and in silico studies. Results: Compound 7a significantly inhibited the growth of HepG2 and PC3 cells for both EGFR wild-type and EGFR(T790M). Compound 7a caused a significant apoptotic effect, arresting HepG2 cells' growth in the S and G2/M phases. Docking and molecular dynamics simulation studies confirmed the correct and stable binding modes of the synthesized compounds against the active sites. Conclusion: Compound 7a is a promising dual EGFR inhibitor for cancer treatment.

Automated summary

This study aimed to discover new thieno[2,3-d]pyrimidine derivatives as EGFR tyrosine kinase inhibitors. Nine derivatives were designed, synthesized, and evaluated in vitro and in silico. Compound 7a showed significant inhibitory effects against both EGFR wild-type and EGFR(T790M), inducing apoptosis and arresting cell growth. Docking and molecular dynamics simulation confirmed the stable binding modes of the synthesized compounds. Compound 7a is a promising dual EGFR inhibitor for cancer treatment.