Rhenium (I)-diselenother (Re-diselenoether) is a\nwater soluble metal-based compound, combining one atom of\nrhenium and two atoms of selenium. This compound has been\nreported to exhibit marked activities against several solid tumor\ncell lines.We now disclose an improved synthesis of this\ncomplex. The Re-diselenoether showed a potent inhibitory\neffect on MDA-MB231 cell division in vitro, which lasted\nwhen the complex was no longer present in the culture. Rediselenoether\ninduced a remarkable reduction of the volume\nof the primitive breast tumors and of the pulmonary metastases\nwithout clinical signs of toxicity, in mice-bearing a MDAMB231\nLuc+ tumor, orthotopically transplanted, after a daily\noral administration at the dose of 10 mg/kg/d. Interestingly, an\nantagonism was observed when cisplatin was administered as\na single i.p. injection 1 week after the end of the Rediselenoether\nadministration. In an effort to gain insight of\nthe mechanisms of action of Re-diselenoether complex, interaction\nwith 9-methylguanine as a nucleic acid base model was\nstudied. We have shown that Re-diselenoether gave both\nmono- and bis-guanine Re adducts, the species assumed to\nbe responsible for the DNA intrastrand lesions.
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