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

Area of Science:

• Oncology
• Pharmacology
• Computational Chemistry

Background:

• Breast cancer remains a leading global cause of mortality.
• Targeted therapies inhibiting cancer cell survival pathways are advancing treatment.
• Novel small molecules are crucial for developing more effective breast cancer therapies.

Purpose of the Study:

• To design and identify small molecule inhibitors targeting key signaling pathways in breast cancer.
• To evaluate the cytotoxic and apoptotic effects of potential drug candidates in vitro.
• To predict the pharmacokinetic properties of identified compounds.

Main Methods:

• Computational approaches including virtual screening and molecular docking.
• In vitro evaluation using MCF7 breast cancer cells for cytotoxicity (IC50) and apoptosis.
• ADMET profiling for pharmacokinetic assessment.

Main Results:

• Two compounds, C12 and C18, showed strong binding to serine-threonine protein kinase and MAP3K5.
• Significant cytotoxic effects were observed with IC50 values of 22.49 µg/ml (C12) and 14.61 µg/ml (C18).
• Apoptosis was confirmed through nuclear condensation, DNA fragmentation, and mitochondrial membrane potential loss; favorable ADMET profiles were predicted.

Conclusions:

• Compounds C12 and C18 demonstrate potent cytotoxic and pro-apoptotic activity against breast cancer cells.
• These compounds represent promising novel therapeutic agents for breast cancer.
• Further in vivo studies are necessary to confirm efficacy and safety.