Antitumor activity of ionic niobocene and molybdenocene complexes in high oxidation states

Abstract

Four air-stable niobocene complexes [(C5H5)2NbCl2]+X- with X = BF4, AsF6, SbF6, SO3CF3 and the molybdenocene derivative [(C5H5)2MoCl2]2+[SbF6]2- were investigated for antitumor properties against Ehrlich ascites tumor in female CF1 mice. All compounds are new, salt-like complexes containing a cationic metallocene moiety, where the early transition metals niobium and molybdenum in the high oxidation states +5 and +6 function as central atoms. The niobocene complexes containing tetrafluoroborate (BF4-) or trifluoromethanesulfonate (CF3SO3-) as anions only induced a maximal cure rate of 50% and led to increases in life span of 182% and 178% following application of optimal doses. The other two niobocene compounds with hexafluoroarsenate (AsF6-) and hexafluoroantimonate (SbF6-) as anions and the molybdenocene derivative [(C5H5)2MoCl2]2+[SbF6]2- effected a maximal cure rate of 100% and increases in life span of 346%, 376%, and 332%, respectively, determined on the key date, i.e., on day 90 after transplantation. On applying the niobocene hexafluoroantimonate complex [(C5H5)2NbCl2] +[SbF6]-, the optimal dose range with a cure rate of 100% was rather broad and extended from 20 mg/kg to 40 mg/kg. Correspondingly, the value of the therapeutic index (TI) was high and amounted to 7.2. In the case of the niobocene hexafluoroarsenate and the molybdenocene hexafluoroantimonate complexes, the TI value decreased to 5.3 and 2.6 respectively. Neither impairments of the general condition nor any conspicuous symptoms could be detected after application of therapeutic doses of the five compounds investigated. Compared to the neutral niobocene dichloro complex [(C5H5)2NbCl2], the therapeutic range of the ionic niobocene derivative [(C5H5)2NbCl2]+[SbF6]- was broadened, the TI value markedly elevated from 2.9 to 7.2, and the toxic symptoms were impressively reduced. The niobocene hexafluoroantimonate complex was the most effective compound investigated in the present study.