Effect of curcumin derivatives on hen egg white lysozyme amyloid fibrillation and their interaction study by spectroscopic methods

Abstract Two novel Boc-L-isoleucine-functionalized curcumin derivatives have been synthesized and characterized, which exhibited enhanced solubility in water compared with the natural curcumin. The solubility could reach 2.12 mg/mL for the monosubstituted compound and 3.05 mg/mL for the disubstituted compound, respectively. Their anti-amyloidogenic capacity on the model protein, hen egg white lysozyme (HEWL), was examined in aqueous solution. ThT fluorescence assay showed that the operation concentration was only 0.5 mM when the inhibition ratio was above 70%. Meanwhile, the inhibitory capacity of monosubstituted curcumin derivative on the formation of HEWL amyloid fibrils was found to be superior to that of disubstituted derivative, suggesting that the phenolic hydroxyl group might contribute to the anti-amyloidogenic activity. Interaction study showed that both curcumin derivatives could bind with HEWL near tryptophan residues and form new ground-state complex before HEWL self-assemblies into amyloid fibrils and thus inhibits the formation of amyloid fibrils. Both of the two cucumin derivatives have displayed low cytotoxicity with HeLa cell.