Ionic rhenocene derivatives with antitumor activity.
The antitumor activity of the three air-stable bis(cyclopentadienyl)rhenium derivatives [(C5H5)2-ReCl2]+Cl-,[(C5H5)2ReCl2]+[AsF6]- , and [(C5H5)2-ReCl2]+[SbF6]- was tested against Ehrlich ascites tumor in female CF1 mice. All three compounds contain the group-7 transition metal rhenium in the +5 oxidation state as their central metal atom. They are ionic, salt-like complexes that are composed of the cationic [(C5H5)2ReCl2]+ moiety and one of the negatively charged counterions Cl-, AsF6-, or SbF6-. Both the chloro and the hexafluoroarsenate complexes induced a maximal cure rate of 100% when given either in a dose range of 120-160 mg/kg (rhenocene trichloride) or at a single dose of 180 mg/kg (hexafluoroarsenate derivative). The hexafluoroantimonate complex effected a maximal cure rate of only 50% at 60 mg/kg. For the two former compounds, the values for the therapeutic index (TI) amounted to 1.7 and 2.1, respectively. No impairment of the general condition or pathologic symptoms in the viscera could be detected by observation of the animals during the days following treatment with therapeutic doses or by autopsy of the surviving animals on the key date (day 90). The rhenocene derivatives investigated in the present study represent a new class of antitumor metallocene compounds as well as the first rhenium(V) complexes exerting cytostatic activity.
Köpf-Maier
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P
Institut für Anatomie, Freie Universität Berlin.
Klapötke
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T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000401:mortality; D003517:Cyclopentanes / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005856:Germ-Free Life; D007928:Lethal Dose 50; D051379:Mice; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000627:therapeutic use* / Q000633:toxicity; D012211:Rhenium / Q000627:therapeutic use* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003517:Cyclopentanes; D009942:Organometallic Compounds; C073784:bis(cyclopentadienyl)rhenium; D012211:Rhenium