Synthesis of Monofunctional Curcumin Derivatives, Clicked Curcumin Dimer, and a PAMAM Dendrimer Curcumin Conjugate for Therapeutic Applications

Abstract

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 curcumin 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 curcumin to various macromolecular scaffolds.

Effect of curcumin on the amyloid fibrillogenesis of hen egg-white lysozyme

“…It has been documented that, due to its radical termination nature, the generation of dimeric form of curcumin has a significant contribution to the antioxidant activity of curcumin [79,80]. Moreover, others have reported that dimeric species of curcumin can selectively destroys human neurotumor cells, suggesting curcumin dimer's critical role in anti-tumor activity [81].…”

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin

“…Their preliminary in vitro biological studies demonstrated that the formulation efficiently stained and dissolved the amyloid fibrils in human heart tissue containing intercellular amyloid. It is to be noted that amyloid-b peptide (Ab) aggregation is suspected to play an important role in Alzheimer's disease and amyloid deposits are also implicated in amyloid heart disease [117].…”

PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase

“…Despite these valuable properties, curcumin's utility is limited due to its lack of solubility in water and its relatively low bioavailability. Nanoparticle-based drug delivery systems such as dendrimers could be helpful in bypassing these problems (Morgan et al, 2003;Bisht et al, 2007;Shi et al, 2007;Anand er al., 2008). Dendrimers are repeatedly branched polymeric molecules with three different parts: an initiator core, the branches and the terminal functional groups (Bharali et al, 2009).…”