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

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 IC50 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. (C)& nbsp;2022 Elsevier B.V. All rights reserved.

Automated summary

The fused heterocyclic ring system of thienopyrimidine scaffold has been widely used in pharmaceuticals to enhance pharmacological and biological activities. In this study, polysubstituted thieno[2,3-d]pyrimidine derivatives were synthesized and tested for their cytotoxic activity against Hela and A549 cancer cell lines. Compound 8c showed promising activity similar to the lead drug Olmutinib, and its binding to EGFR kinase differed from Olmutinib. The preliminary structure-activity relationship suggested that introducing oxygen substituents favored antitumor activity.