Pyridine‐Based Azachalcones as Potent Anti‐Breast Cancer Agents: Synthesis, In Vitro Evaluation, and In Silico Insights

Abstract This study explores pyridine‐based azachalcones as potential anti‐breast cancer agents. Synthesized via piperidine‐catalyzed Claisen–Schmidt condensation, these compounds exhibited high yields and significant in vitro activity against MDA‐MB‐231 and MCF‐7 cell lines, with minimal toxicity toward normal cells. Compound 3b demonstrated the most potent effect (IC 50 = 9.96 µM against MDA‐MB‐231), surpassing tamoxifen. In silico studies revealed strong binding affinities to VEGFR‐2 and EGFR, supported by molecular dynamics simulations indicating stable interactions and favorable MMGBSA binding energies. ADMET profiling predicted good drug‐likeness and safety. These findings position azachalcones as potential lead scaffolds for breast cancer therapy and provide a strong foundation for future preclinical investigations.