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Curcumin analog cytotoxicity against breast cancer cells: exploitation of a redox-dependent mechanism

Authors
Journal
Bioorganic & Medicinal Chemistry Letters
0960-894X
Publisher
Elsevier
Publication Date
Volume
19
Issue
23
Identifiers
DOI: 10.1016/j.bmcl.2009.10.023
Keywords
  • Curcumin Analogs
  • Glutathione
  • Anti-Cancer
  • Pro-Drug

Abstract

Abstract A series of novel curcumin analogs, symmetrical dienones, were previously shown to possess cytotoxic, anti-angiogenic and anti-tumor activities. Analogs 1 (EF24) and 2 (EF31) share the dienone scaffold and serve as Michael acceptors. We propose that the anti-cancer effects of 1 and 2 are mediated in part by redox-mediated induction of apoptosis. In order to support this concept, 1 and 2 were treated with l-glutathione (GSH) and cysteine-containing dipeptides under mild conditions to form colorless water-soluble adducts, which were identified by LC/MS. Comparison of the cytotoxic action of 1, 2 and the corresponding conjugates, 1-(GSH) 2 and 2-(GSH) 2, illustrated that the two classes of compounds exhibit essentially identical cell killing capabilities. Compared with the yellow, somewhat light sensitive and nearly water insoluble compounds 1 and 2, the glutathione conjugates represent a promising new series of stable and soluble anti-tumor pro-drugs.

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