Design and Synthesis of Pyrazole‐Curcumin Hybrids as Dual‐Function Agents: Antibacterial, Antitumor, and Molecular Docking

ABSTRACT Pyrazole derivatives are prominent in medicinal chemistry for their antimicrobial and anticancer properties, yet face synthetic limitations. Curcumin analogs exhibit bioactivity but suffer from poor stability. This study designed novel pyrazole‐curcumin hybrids by incorporating indole moieties to optimize hydrogen bonding and hydrophobic interactions, aiming to develop dual‐function agents. A series of 12 compounds ( 2a – 2i , 3a – 3c ) were synthesized via aldol condensation and cyclization, with methodological innovations like solvent optimization (e.g., methanol‐acetic acid) and N 2 protection control to enhance efficiency. Biological evaluations demonstrated broad‐spectrum antibacterial activity against E. coli and B. subtilis ; compound 2f showed inhibition zones of 15 and 25 mm, surpassing palmatine. In antitumor assays, hybrid 3a was potent against Eca109 and MGC803 cancer cells (IC 50 values of 15.79 µM and 11.02 µM), outperforming curcumin. Molecular docking revealed strong binding of 3a to EGFR and CDK6 targets (both of −9.6 kcal/mol), supported by hydrophobic and hydrogen‐bond interactions. These findings highlight the hybrids' potential as versatile therapeutics, providing a foundation for future drug development.