THE CYTOTOXICITY OF ADENOSINE 5'-[N,N-DI-(GAMMA-O-CARBORANYL)PROPYL] PHOSPHORODIAMIDATE IN HUMAN TMOLT(3) LEUKEMIC-CELLS

Adenosine 5'-[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate 1 was successfully synthesized and characterized. The compound demonstra ted potent in vivo antineoplastic activity and in vitro cytotoxicity i n murine and human leukemia and uterine carcinoma tumor cell lines. In human T cell leukemia DNA preferentially was inhibited with key enzym es in the purine pathway being effectively inhibited by the agent. Mar ginal inhibition of the activities DNA polymerase alpha, carbamyl phoi sphate synthetase, nucleoside kinase, and thymidylate synthetase was o bserved. Tmolt(3) DNA strand scission was observed after 24 hr. incuba tion with compound 1 to 100 mu M.