title: Synthesis, X-ray structure, interactions with DNA, remarkable in vivo tumor growth suppression and nephroprotective activity of cis-tetrachloro-dipivalato dirhenium(III).
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.
authors.affiliation: Department of Biophysics and Biochemistry, Dnipropetrovs'k National University, Gagarin Ave. 72, Dnipropetrovs'k 49050, Ukraine. Electronic address: n.shtemenko@i.ua.
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Shtemenko
authors.forename: Helen T
authors.initials: HT
authors.lastname: Chifotides
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Domasevitch
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Golichenko
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Babiy
authors.forename: Zhanyong
authors.initials: Z
authors.lastname: Li
authors.forename: Katherina V
authors.initials: KV
authors.lastname: Paramonova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Shtemenko
authors.forename: Kim R
authors.initials: KR
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012211:Rhenium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012211:Rhenium; D002945:Cisplatin
keywords: Combination therapy; DNA cleavage; Dirhenium; Tumor suppression