Five ionic cyclopentadienyltitanium (IV) derivatives were investigated for their activity against fluid
Ehrlich ascites tumor. Four compounds were built up by the intact bis(cyclopentadienyl)
titanium(IV) ("
titanocene") unit, forming the cationic moiety together with two covalently bound
ligands, with certain
anions being bonded via electrostatic forces: the
acetonitrile complex [(C5H5)2TiCl(NCCH3)]+[FeC14]- (I), the 2'2'-bipyridyl derivative [(C5H5)2Ti(bipy)]2+[CF3SO3]2 (II), the
o-phenanthroline complex [(C5H5)2Ti(phen)]2+[CF3SO3]2 (III), and the N-methyl-o-aminothiophenolate derivative [(C5H5)2Ti[o-S(NACH3)C6H4]]+I- (IV). Another ionic cyclopentadienyltitanium derivative investigated was the five-coordinate bis(dithiolene) chelate (C5H5)Ti(1,2,4-S2C6H3CH3)2]-N(C2H5)4)+ (V), the cyclopentadienyltitanium moiety representing the anionic part of the complex
salt. All complexes were ionic,
salt-like compounds, distinguished by good water solubility. Whereas complexes I, III, and V, given at optimal dose levels, effected maximal cure rates of only 70%-80%, all animals were cured after receiving complexes II and IV at dose ranges of 200-220 and 240-300 mg/kg, respectively. The antitumor activity of complex I was confirmed against solid experimental
tumor systems
B16 melanoma, colon 38
carcinoma, and Lewis lung
carcinosarcoma. Because of their improved solubility in water and pronounced antitumor activity (especially that of II and IV against fluid
Ehrlich ascites tumor), ionic cyclopentadienyl
titanium complexes are considered to be an interesting new type of
antitumor agent.