Abstract

Curcumin analogue compounds derived from benzaldehyde moieties originating from p-dimethylaminebenzaldehyde namely (1E,4E)-1,5-bis[4-(dimethylamino)phenyl]penta-1,4-dien-3-one (A1) and (3E,5E)-1-benzyl-3,5-bis[[4-(dimethylamino)phenyl]methylidene]piperidin-4-one (A2), were synthesized through a base-catalyzed condensation using a sonication method. The reaction proceeded to afford a yellow crystalline product in 74.31% and 91.02% yield. The synthesized compounds were fully characterized using ATR-IR, ¹H-NMR, and ¹³C-NMR. In addition, in silico studies were performed to evaluate the binding affinity of the curcumin analogues against key cancer-related proteins, including EGFR, Bcl-2, and p53 mutant, using AutoDock Vina. Docking results revealed that the analogues (A1 and A2) exhibited higher binding affinity toward EGFR and mutant p53 compared to curcumin and the native ligands. For Bcl-2, the analogues displayed a binding affinity higher than curcumin but lower than the native ligand. The in vitro cytotoxicity of the synthesized compounds was evaluated using the MTT assay on T47D breast cancer cells and normal Vero cells. The curcumin analogues (A1 and A2) demonstrated very strong cytotoxic activity with an IC₅₀ of 10.09 μg/mL and 7.66 μg/mL while curcumin exhibited an IC₅₀ of 4.010 μg/mL. Both compounds showed high selectivity toward cancer cells over normal cells. These findings indicate that the synthesized curcumin analogue possesses promising anticancer potential supported by both computational and biological evaluations.

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