Synthesis, X-ray structure, interactions with DNA, remarkable in vivo tumor growth suppression and nephroprotective activity of cis-tetrachloro-dipivalato dirhenium(III).
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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--pivalatodirhenium(III), cis-Re2[(CH3)3CCOO]2Cl42(CH3)2SO (I). The interactions of I with DNA were also investigated by electrophoretic mobility shift assays, electronic absorption titrations, Tm and viscosity measurements, which indicate that compound I interacts relatively strongly with the DNA (Kb 2.210(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.
Shtemenko, N. I., Chifotides, H. T., Domasevitch, K. V., Golichenko, A. A., Babiy, S. A., Li, Z., ... Dunbar, K. R.
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Shtemenko, Natalia I||Chifotides, Helen T||Domasevitch, Konstantin V||Golichenko, Alexander A||Babiy, Svetlana A||Li, Zhanyong||Paramonova, Katherina V||Shtemenko, Alexander V||Dunbar, Kim R
