Document Type : Research Articles
Authors
1
JSS College of Pharmacy, Najwal, Vijaypur, Jammu, India.
2
Department of Pharmaceutics, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
3
Associate Professor, Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, Ooty, JSS Academy of Higher Education & Research, Mysuru, India.
4
Associate Professor (Pharmacy Practice), Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, South Africa.
5
Assistant Professor, MET College of Pharmacy, Nashik, Maharashtra, India.
6
Faculty of Health Sciences, School of Pharmacy, JSS Academy of Higher Education and Research, Mauritius.
Abstract
Background: Breast 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. Methods: A 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. Results: Two 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. Conclusion: The 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.
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