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

The glutathione conjugates of curcumin analogs represent a promising new series of stable and soluble anti-tumor pro-drugs. 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) s...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-12, Vol.19 (23), p.6627-6631
Main Authors: Sun, Aiming, Lu, Yang J., Hu, Haipeng, Shoji, Mamoru, Liotta, Dennis C., Snyder, James P.
Format: Article
Language:English
Subjects:
Anti-cancer
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Breast Neoplasms - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Curcumin - analogs & derivatives
Curcumin - chemistry
Curcumin - pharmacology
Curcumin analogs
Drug Screening Assays, Antitumor
General aspects
Glutathione
Humans
Medical sciences
Molecular Structure
Oxidation-Reduction
Pharmacology. Drug treatments
Pro-drug
Stereoisomerism
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Summary:The glutathione conjugates of curcumin analogs represent a promising new series of stable and soluble anti-tumor pro-drugs. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.10.023