| Abstract | The thioamido function of [CuCl2(1H)]Cl (2) (1=4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole), a cytotoxic copper complex, was converted into thioether moieties, leading to the synthesis of [CuCl2(3)]2 (4) and [CuCl2(5)] (6) (3=6-methyl-3-pyridin-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine; 5=4-amino-5-ethylthio-3-(2-pyridyl)-1,2,4-triazole). These complexes were structurally characterized, and their stability constants, along with their biological activity, were determined. 4 and 6 were slightly less stable and significantly less active than 2. However, as 2, both complexes induced nonapoptotic vacuolar cell death. Copper uptake, investigated in both 2-sensitive and -insensitive cell types, was markedly higher in sensitive cells where it was associated with an increase in oxidized glutathione. These data suggest that the thioamido function enhances the cytotoxicity of copper complexes in cancer cells promoting the accumulation of the metal and its interaction with cell thiols. |
| Authors | Saverio Tardito, Ovidio Bussolati, Monica Maffini, Matteo Tegoni, Marco Giannetto, Valeria Dall'asta, Renata Franchi-Gazzola, Maurizio Lanfranchi, Maria Angela Pellinghelli, Claudio Mucchino, Giovanni Mori, Luciano Marchio
(Affiliation: Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica, Chimica Fisica, Università degli Studi di Parma, Viale G.P. Usberti 17/A, 43100 Parma, Italy.)
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| Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 50
Issue 8
Pg. 1916-24
(Apr 19 2007)
ISSN: 0022-2623 United States |
| PMID | 17373781
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Antineoplastic Agents
- Chelating Agents
- Organometallic Compounds
- Reactive Oxygen Species
- Triazoles
- Copper
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| Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Cell Line, Tumor
- Chelating Agents
(chemistry)
- Copper
- Crystallography, X-Ray
- Drug Screening Assays, Antitumor
- Humans
- Models, Molecular
- Molecular Structure
- Organometallic Compounds
(chemical synthesis, chemistry, pharmacology)
- Oxidative Stress
- Reactive Oxygen Species
(metabolism)
- Structure-Activity Relationship
- Triazoles
(chemical synthesis, chemistry, pharmacology)
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