Figure 1.
Structure/function assessment of curcumin analogs.
Quantitative assessment of 20 curcumin analogs for inhibitory activity of Aβ aggregation and comparison with chemical substitutions made to the curcumin structure.
Figure 2.
Structures of active analogs of curcumin.
The analogs shown were identified as those that inhibited Aβ oligomerization equal to or better than curcumin (data obtained from Figure 1; inhibitory activity ≥50% within one S.D. of mean values). These analogs include 7 compounds from the 7-carbon series and 13 compounds from the 5-carbon series.
Figure 3.
Quantitative comparison of curcumin with analogs 1, 2, and 8 as Aβ oligomerization inhibitors.
Soluble Aβ monomeric peptide was prepared as described in methods and diluted to a final concentration of 200 nM directly into phosphate buffered saline (PBS), pH 7.4, or PBS containing the indicated concentrations of curcumin or analogs 1, 2 or 8. Reactions were incubated at 37°C for 24 h. Oligomers were quantified by capture ELISA. All reactions were prepared in triplicate to calculate mean values. Standard deviations from mean values were calculated and amounted to <5% for each experimental point.
Figure 4.
Quantitative assessment of cytotoxic effects of curcumin and compound 2 on murine microglial cells.
Cultured microglial cells were incubate without or with the indicated concentrations of curcumin or compound 2 for 24 h. Cells were then incubated with Wst-1 reagent for 1 h, afterwhich absorbance was measured (460 nm). Values on graph represent mean values calculated from triplicate experimental points. Standard deviations from mean values were determined as <5% for each experimental point.
Figure 5.
Comparison of chemical structures and IC50 values of analogs demonstrating improved bioactivity as Aβ oligomerization inhibitors.
Compound 2 represents an improvement of approximately 6–7 fold over Aβ aggregation inhibitory activity of curcumin.