Abstract |
In this study we report the synthesis, the X-ray crystal structure and the in vivo tumor growth suppression and nephroprotective activity of bis- dimethylsulfoxide-cis-tetrachlorodi-μ-pivalatodirhenium(III), cis-Re2[(CH3)3CCOO]2Cl4·2(CH3)2SO (I). The interactions of I with DNA were also investigated by electrophoretic mobility shift assays, electronic absorption titrations, ΔTm and viscosity measurements, which indicate that compound I interacts relatively strongly with the DNA (Kb 2.2×10(3)M(-1)), most likely by forming covalent interstrand cross-links, and by kinking and unwinding supercoiled DNA; moreover, DNA cleavage by I is enhanced in the presence of redox-active species. The in vivo antitumor activity of I is considerable and is accompanied by significant elimination of red blood cell and kidney damage. Remarkably, compound I in combination with cisplatin (combined Re-Pt antitumor system) led to suppression of tumor growth or complete tumor elimination. The antihemolytic and nephroprotective abilities of I only or as a part of the Re-Pt antitumor system were established and a possible mechanism for the influence of I on these properties, involving erythropoietin production, is proposed.
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Authors | Natalia I Shtemenko, Helen T Chifotides, Konstantin V Domasevitch, Alexander A Golichenko, Svetlana A Babiy, Zhanyong Li, Katherina V Paramonova, Alexander V Shtemenko, Kim R Dunbar |
Journal | Journal of inorganic biochemistry
(J Inorg Biochem)
Vol. 129
Pg. 127-34
(Dec 2013)
ISSN: 1873-3344 [Electronic] United States |
PMID | 24121302
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013. |
Chemical References |
- Antineoplastic Agents
- DNA, Neoplasm
- Rhenium
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Cisplatin
(chemistry, pharmacology)
- Crystallography, X-Ray
- DNA, Neoplasm
(chemistry, metabolism)
- Drug Screening Assays, Antitumor
- Neoplasms, Experimental
(drug therapy, metabolism, pathology)
- Oxidation-Reduction
- Rats
- Rats, Wistar
- Rhenium
(chemistry, pharmacology)
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