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Synthesis and Biological Evaluation of Curcumin-Nitroxide-Based Molecular Hybrids as Antioxidant and Anti-Proliferative Agents

[ Vol. 13 , Issue. 8 ]

Author(s):

Balazs Bognar, M. Lakshmi Kuppusamy, Esha Madan, Tamas Kalai, Maria Balog, Jozsef Jeko, Periannan Kuppusamy and Kalman Hideg*   Pages 761 - 772 ( 12 )

Abstract:


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 activity.

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.

Keywords:

Antioxidants, anti-proliferative compounds, curcuminoids, nitroxides, Pabon reaction, structure-activity relationship.

Affiliation:

Institute of Organic and Medicinal Chemistry, University of Pecs, Szigeti st. 12. Pecs, H-7624 Pecs, Department of Radiology, Geisel School of Medicine, Dartmouth College, Rubin-601, One Medical Center Drive, Lebanon, NH 03756, Department of Radiology, Geisel School of Medicine, Dartmouth College, Rubin-601, One Medical Center Drive, Lebanon, NH 03756, Institute of Organic and Medicinal Chemistry, University of Pecs, Szigeti st. 12. Pecs, H-7624 Pecs, Institute of Organic and Medicinal Chemistry, University of Pecs, Szigeti st. 12. Pecs, H-7624 Pecs, Department of Chemistry, College of Nyiregyhaza, Sostoi st. 31/B, H-4440 NyĂ­regyhaza, Department of Radiology, Geisel School of Medicine, Dartmouth College, Rubin-601, One Medical Center Drive, Lebanon, NH 03756, Department of Organic and Medicinal Chemistry, Medical Faculty of University of Pecs, Szigeti st. 12. Pecs

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