Selected Thieno[2,3-d] Pyrimidine Derivatives Target Breast Cancer Cell Proliferation and Membrane Organization

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, highlighting the urgent need for novel therapeutic agents with improved efficacy and selectivity. In this study, we investigated the anticancer potential of selected thieno[2,3-d]pyrimidine-based hybrids in breast cancer cell models with different metastatic potential. The compounds were evaluated for their effects on cell viability, clonogenic survival, migration, cell-cycle progression, cytoskeletal organization, and plasma membrane organization. Several derivatives exhibited concentration-dependent antiproliferative activity, inhibited colony formation and cell migration, disrupted cytoskeletal integrity, and modulated plasma membrane organization. Cell-cycle analysis revealed compound- and cell line-dependent alterations in the distribution of cells across the G1, S, and G2/M phases. Among the tested compounds, derivatives 1, 5, and 6 displayed the most favorable biological profiles, combining antiproliferative activity with moderate selectivity toward breast cancer cells, whereas compound 2 exerted the most pronounced effects on plasma membrane organization and cell migration. Collectively, these findings identify selected thieno[2,3-d]pyrimidine-based hybrids as promising lead compounds for the development of novel anticancer agents targeting both tumor cell proliferation and plasma membrane organization.