Background: Natural products and their derivatives are widely used to treat cancer and
other diseases associated with ROS- and RNS-induced damages.
Methods: A series of paramagnetic modified curcumin analogs and 3,5-diarylidene-piperidones
(DAP) have been designed, synthesized, and characterized on their anti-proliferative and antioxidant
Results: Biological characterization of the new compounds supported the earlier results that incorporation
of a nitroxide moiety or its precursor into curcumin or diarylidenylpiperidone (DAP) scaffolds
resulted in anti-proliferative effect toward cancerous cell-lines in case of aryl hydroxy and/or
methoxy substituent containing derivatives, suggesting their potential for targeted therapeutic applications.
In case of basic side chain derivatives, nitroxide incorporation gave unambiguous results, however
in tendency the more accessible DAP derivatives had stronger anti-proliferative effect. In most
cases, the nitroxide incorporation increased the TEAC value (proton and electron donation capability)
of DAP derivatives.
Conclusions: Among the compounds synthesized and investigated the spin-labeled curcumin and
3,5-bis(4-hydroxy-3-methoxybenzylidene)piperidin-4-one derivatives were the most effective antiproliferative
and antioxidant derivatives.