Optimizing adamantane derivatives for enhanced EGFR inhibition in MCF-7 breast cancer cells

Uppar, Pradeep M. and Harish, K. K. and Beeraka, N. M. and Xi, Zhang and Mahendra, M. and Mamatha, S. K. and Sindhu, M. P. and Lobie, Peter E. and Rangappa, K. S. and Pandey, Vijay and Basappa, B. (2025) Optimizing adamantane derivatives for enhanced EGFR inhibition in MCF-7 breast cancer cells. Journal of Molecular Structure, 1331. ISSN 0022-2860

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Abstract

Epidermal growth factor receptor (EGFR) is a key target in breast cancer (BC) treatment due to its significant role in disease progression. This study aims to synthesize novel heterocyclic compounds by tailoring adamantane with pyrazoline followed by piperazines to target EGFR in breast cancer cells. Synthesis of the heterocyclic compounds was performed by Claisen-Schmidt reaction followed by cyclization and concludes with substitution by secondary amines. Structure of the lead compound 1-(3-((3r,5r,7r)-adamantan-1-yl)-5-(4-nitrophenyl)-4,5-dihydro1H-pyrazol-1-yl)-2-(4-(2-nitrophenyl)piperazin-1-yl)ethenone (6c) is confirmed by HRMS, 1H & 13C NMR, IR and Single crystal XRD. In silico docking studies were performed to investigate the molecular interactions of the compound 3, 4 & 6c with the EGFR binding site and to calculate their binding energies. Molecular dynamics simulations were conducted to explore stability of protein-ligand complex for compound 6c within the active site groove of EGFR protein in comparison with its precursors. Additionally, cytotoxic effects of these compounds against MCF-7 breast cancer cells were evaluated using IC-50 assays. Among the synthesized compounds, 6c exhibited significant cytotoxic effects against MCF-7 cells, with IC-50 values of 1.22 mu M. Compound 6c had binding energy of-8.6 kcal/mol, indicating strong interactions within the EGFR binding site indicating their anti- breast cancer potential.

Item Type:	Article
Uncontrolled Keywords:	Adamantane, Breast cancer, EGFR, Piperazine, Pyrazoline
Subjects:	C Chemical Science > Organic Chemistry
Divisions:	Department of > Organic Chemistry
Depositing User:	Ms Varalakshmi
Date Deposited:	04 Nov 2025 10:41
Last Modified:	04 Nov 2025 10:41
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17906

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