Antitumor activity of mono- and dimetallic transition metal carborane complexes of Ta, Fe, Co, Mo, or W

Complexes containing Ta, Fe, Co, Mo, or W metal centers that are bound to C 2B4 or C2B3 small carborane ligands proved to be potent cytotoxic agents in murine and human tissue cultured cells, being more effective in suspended leukemia and lymphomas but surprisingly also effective against the growth o f selected solid tumors. These complexes inhibited nucleic acid metabolism, specifically DNA and purine de novo syntheses. Key enzyme activities in nu cleic acid metabolism which were inhibited by the complexes were P388 DNA p olymerase a, ribonucleotide reductase, dihyrofolate reductase, PRRP-amidotr ansferase and IMP dehydrogenase. The complexes afforded a moderate amount o f DNA-fragmentation in P388 lymhocytic leukemia cells and were moderate inh ibitors of human DNA topoisomerase II activity; however, the DNA molecule i tself was not a target of the complexes in that there was no evidence that the complexes caused intercalation between base pairs, caused cross-linking of the strands of DNA or alkylated the bases of DNA.