Efficient synthesis and cytotoxic activity of polysubstituted thieno[2,3-d]pyrimidine derivatives.

• Polysubstituted thienopyrimidine derivatives were designed and synthesized. • Compound (8c) showed significant activities against studied cancer cell lines. • Molecule (8c) docked with EGFR kinase to study its interaction with the anticancer enzyme. • SAR was preliminarily discussed through cytotoxic activity data and analysis of molecular docking. Thienopyrimidine scaffold is a fused heterocyclic ring system that has been found to be an integral part of pharmaceutical products to the improvement of pharmacological and biological activities. A series of polysubstituted thieno[2,3- d ]pyrimidine derivatives have been synthesized and tested for their cytotoxic activity against Hela and A549 cancer cell lines in which EGFR is highly expressed. Most of the target compounds 8a-8e showed excellent activity against Hela and A549 cancer cell lines. The most promising compound 8c exhibited the similar IC 50 values on A549 cell lines to the lead drug Olmutinib. The molecular docking results indicated that compound 8c bound to EGFR kinase in a different method with Olmutinib. The preliminary structure-activity relationship (SAR) suggested that the introduction of oxygen substituents was more favorable for antitumor activity. Compound 8c proved to be a promising antitumor agent. [Display omitted] [ABSTRACT FROM AUTHOR]