Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials Poster Session I

42-POS Board 42 Curcumin Analogues in Treatment of Alzheimer’s Disease Katarina Siposova 1 , Erika Ferrari 2 , Rois Benassi 2 , Monica Saladini 2 , Giulia Ortega 2 , Zuzana Bednarikova 1 , Zuzana Gazova 1 . 1 Institute of experimental physics, Kosice, Slovakia, 2 Universituy of Modena and reggio Emilia, Italy, Modena, Italy. Current treatment of Alzheimer's disease leads to moderate symptomatic benefits but not to stop disease progression. Curcumin and its derivatives have attracted great interest in the prevention and treatment of Alzheimer’s disease (AD), due to the ability inhibit the formation of amyloid- beta (Aβ) aggregates and the ability to bind Cu (II) ion. However, the use of curcumin in vivo is limited by its poor bioavailability, instability, and reduced water solubility. We have examined the anti-amyloid activity of newly synthesized curcumin derivatives (curcuminoids) with greater chemical stability comparing to curcumin, while maintaining almost unchanged biological properties of the lead compound. The K2T derivatives were synthesized by introducing the t- butyl ester group on central atom of the diketo moiety and different substituent on the phenyl rings of curcumin frame. The IC50 values determined from the dose-response curves obtained by fitting the average Thioflavin fluorescence assay values by non-linear least-square method were in micromolar range. The character of the aggregates was examined also by atomic force microscopy. The imbalances of metal ions homeostasis, especially Cu2+, may favor Aβ aggregation and induce oxidative damage. Thus, our second goal was to examine the ability of curcuminoids to bind Cu2+ ions and therefore, to evaluate their antioxidant activity. It was shown that K2T compounds effectively binds Cu2+. It was also demonstrated that K2T21 and in some extent K2T31 hold the capacity to scavenge DPPH radicals suggesting the importance of a phenolic group combined with methoxyl moiety in orto position. We concluded that the curcumin derivative K2T21 due to its ability to inhibit Aβ aggregation and bind to Cu2+ together with good radical scavenging properties is the best candidate for designing new curcumin-based analogs that can effectively treat AD. Acknowledgement: This work was supported by grants VEGA 0181, ESF 26110230097.

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