Design, synthesis, molecular docking and biological evaluation of a novel β-lactam derivative with anti-breast cancer activity

Khaleel, Luay Ali; Chfat, Hayder Ghanim

doi:10.22034/crl.2025.521462.1588

Design, synthesis, molecular docking and biological evaluation of a novel β-lactam derivative with anti-breast cancer activity

Document Type : Research Article

Authors

Luay Ali Khaleel ¹

Hayder Ghanim Chfat ²

¹ Department of Chemistry, College of Science, University of AL-Qadisiyah, Al Diwaniyah, Iraq.

² Jabir Ibn Hayyan University for Medical and Pharmaceutical Sciences, Faculty of Medical Science, Najaf, Iraq

https://doi.org/10.22034/crl.2025.521462.1588

Abstract

This study presents the synthesis and characterization of Azo, Schiff base, and novel β-lactam derivatives. The Azo derivative (A1) was synthesized by coupling the diazonium salt prepared by dissolving 2-(aminomethyl)aniline in acidic medium at (0-5)°C with 4,5-diphenyl-1H-imidazole. The Schiff base derivative (S1) was then synthesized by reacting the Azo derivative prepared in the previous step with 3-phenyl-1H-pyrazole-4-carbaldehyde. Finally, the β-lactam derivative (B1) was prepared by reacting the Schiff base derivative prepared in the second step with triethylamine and Chloroacetyl chloride. The structural characterization of the synthesized compounds was carried out using (FT-IR), (1H-NMR) and (13C-NMR) spectroscopy. The molecular docking of the beta-lactam derivative against the breast cancer-associated MCF-7 protein was studied, revealed a binding affinity of (−8.78kcal/mol), indicating a strong interaction between the ligand and the target protein. Furthermore, the root-mean-square deviation (RMSD) value of (2.40Å) suggests a stable and consistent binding conformation within the active site indicating strong potential as an anticancer agent. Biological assays demonstrated selective toxic activity against MCF-7 breast cancer cells with an IC₅₀ of (102.2μg/mL), while showing less toxicity to normal WRL-68 cells (IC₅₀ = 230.1μg/mL).

Graphical Abstract