Synthesis and antiproliferative evaluation of novel 3,5,8-trisubstituted coumarins against breast cancer

Abstract

<b>Aim:</b> This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. <b>Results:</b> The synthesized compounds, particularly compound <b>5</b>, exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound <b>5</b> altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIβ expression. Molecular modeling indicated compound <b>5</b>'s strong affinity for EGFR, human EGF2 and topoisomerase II proteins. <b>Conclusion:</b> These findings highlight compound <b>5</b> as a multifaceted antitumor agent for breast cancer.