Synthesis of monofunctional curcumin derivatives, clicked curcumin dimer, and a PAMAM dendrimer curcumin conjugate for therapeutic applications

Curcumin, the primary active ingredient in the spice turmeric, was converted to reactive monofunctional derivatives (carboxylic acid/azide/ alkyne). The derivatives were employed to produce a 3 + 2 azide-alkyne clicked curcumin dimer and a poly(amidoamine (PAMAM) dendrimer-curcumin conjugate. The monofunctional curcurnin derivatives retain biological activity and are efficient for labeling and dissolving amyloid fibrils. The curcumin dimer selectively destroys human neurotumor cells. The synthetic methodology developed affords a general strategy for attaching curcurnin to various macromolecular scaffolds.