Novel curcumin analogs targeting TNF-induced NF-κB activation and proliferation in human leukemic KBM-5 cells

Novel curcumin analogs were synthesized using Knoevenagel condensation to convert enolic diketones of curcumin into non-enolizable ones and Schiff bases were prepared using a bioactive thiosemicarbazide pharmacophore. Copper(II) conjugates of all synthesized ligands were prepared and structurally characterized as well as evaluated for their potential of inhibiting TNF-induced NF-κB activation and proliferation in human leukemic KBM-5 cells wherein compound 13 was found to be more potent than curcumin. Compounds were further examined on other tumor cell lines such as Jurkat, H1299, and MM1, respectively.

The work describes new curcumin analogs targeting NF-κB protein, where the diketo motif is functionalized through Knoevenagel condensation at the active methylene site yielding Schiff base ligands. Conjugation with copper shows synergistic enhancement in the inhibitory activity of these ligands.Figure optionsDownload as PowerPoint slide