Synthesis, characterization, crystal structure and anti-proliferative properties of curcumin mimic conjugates

Three novel 4-piperidone-based derivatives (<b>3a–c</b>) were synthesized utilizing the base-catalyzed condensation method (KOH/EtOH) with aromatic aldehydes (<b>2a–c</b>) featuring secondary amine rings, specifically piperidine, morpholine, and methyl piperazine. The three newly synthesized derivatives were characterized through X-ray crystallography, and their anti-proliferative effects were assessed against three different human cancer cell lines: breast carcinoma (MCF-7), liver cancer (HepG-2), and colorectal carcinoma (HCT-116), along with a normal cell line (RPE1), following the MTT assay procedure. Among them, compound <b>3c</b> demonstrated the highest efficacy against all tested cell lines, demonstrating IC₅₀ = 1.07 ± 0.04 μM for MCF-7 and 2.55 ± 0.07 μM for HepG-2, compared to the standard reference, Doxorubicin, which had IC₅₀ = 5.38 ± 0.05 μM and 4.25 ± 0.01 μM, respectively. Moreover, a molecular docking study confirmed the stable interaction of compound <b>3c</b> within the ATP binding site of human cyclin-dependent kinase 2 (CDK2). This study introduces three promising intermediates for further research in medicinal chemistry.