In Silico and In Vitro Evaluation of Novel Small Molecule Inhibitors Targeting Apoptosis Pathways in Breast Cancer Cells.

backgroundBreast cancer is one of the leading causes of cancer-related mortality globally. Recent advances in targeted therapies have focused on selectively inhibiting signalling pathways that are vital for cancer cell survival and proliferation. Identifying novel small molecules with such inhibitory capabilities remains a critical step toward more effective treatments.

methodsA computational approach was utilized to design and identify small molecule inhibitors targeting key signalling pathways implicated in breast cancer progression. Virtual screening and molecular docking analyses were conducted to identify potential lead compounds. The selected compounds were further evaluated in vitro using MCF7 breast cancer cells to determine cytotoxicity (via IC50) and to assess apoptotic effects. ADMET profiling was performed to predict pharmacokinetic properties.

resultsTwo lead compounds, C12 and C18, demonstrated strong binding affinities to serine-threonine protein kinase and MAP3K5, both of which are critical regulators of apoptosis. In vitro studies revealed significant cytotoxic effects, with IC50 values of 22.49 ± 1.01 µg/ml for C12 and 14.61 ± 0.01 µg/ml for C18. Microscopic and biochemical analyses showed hallmark features of apoptosis, including nuclear condensation, DNA fragmentation, and mitochondrial membrane potential loss. ADMET predictions indicated favourable pharmacokinetic profiles for both compounds.

conclusionThe identified compounds C12 and C18 exhibit potent cytotoxic and pro-apoptotic activity in breast cancer cells, highlighting  their potential as promising novel therapeutic agents. However, further in vivo studies are essential to validate their efficacy and safety profiles.