Design, Synthesis, Characterization, and Anti-Breast Cancer Activity of Novel Pyrazole-Based Chalcones: Insights from Molecular Docking and DFT Studies

Abstract

A novel series of 1-(furan-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one was designed, synthesized, and characterized with the aim of developing potential anti-breast cancer agents. The synthesis was carried out by a Claisen-Schmidt condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde with 2-acetylfuran in the presence of ethanolic sodium hydroxide under reflux conditionS for 7- 8 hours. The resulting chalcone derivative was purified and confirmed by TLC, Melting point, and Spectroscopic techniques, including IR, 1H-NMR, 13C-NMR, and Mass Spectroscopy. The biological evaluation of the synthesized compounds was performed against the MCF-7 breast cancer cell line, where the compounds exhibited varying degrees of cytotoxic activity, with some derivatives showing promising anti-cancer potential. Furthermore, molecular docking studies were conducted to investigate their binding interactions with breast cancer target proteins. In addition to docking, Density Functional Theory (DFT) studies were carried out to investigate the electronic properties and chemical reactivity of the compounds. DFT calculations provided crucial parameters such as the HOMO-LUMO energy gap, molecular electrostatic potential (MEP) maps, dipole moments, and global reactivity descriptors (e.g., electronegativity, hardness, softness).These theoretical insights help in understanding the structure–activity relationships (SAR) and in predicting the stability and reactivity of the compounds at the molecular level. The results suggest that structural modifications in the pyrazole-furan chalcone framework can significantly influence biological activity.