THE INFLUENCE OF POLYETHER SUBSTITUENTS ON BIOLOGICAL ACTIVITY OF CURCUMIN DERIVATIVES

Curcumin is reported as an anti-proliferative and chemopreventive compound. However, it shows poor water solubility, low bioavailability, and rapid metabolism. To address these problems, curcumin derivatives substituted with polyether chain were synthesized to improve the hydrophilicity of curcumin and thus its bioavailability. The biological activity of modified curcumin molecules were studied with human normal Blymphocytes GM 14667 and human leukemia cells HL60 and covered: the denotation of IC50 values for each new compound with use of MTT test and the studies on apoptosis induction observed as morphological changes and the expression of apoptotic proteins, BAX, BCL-2 and survivin with use of Western Blot analysis. All effects were referenced to native curcumin. The derivatives with modified polyether chains number and the position of methoxy groups were selected for further studies. As was shown, the solubility of the compound does not directly correlate with its cytotoxicity. The maintenance of the methoxy group in the meta position, as well as the introduction of hydrophilic polyether chains but not the number of polyether chains, may affect the cytotoxic activity of curcumin derivatives against cancer cells. Modifications of the curcumin molecule structure can determine its impact on the profile of pro- or anti-apoptotic proteins.