Ih. Hall et al., THE CYTOTOXICITY OF ADENOSINE 5'-[N,N-DI-(GAMMA-O-CARBORANYL)PROPYL] PHOSPHORODIAMIDATE IN HUMAN TMOLT(3) LEUKEMIC-CELLS, Anticancer research, 17(1A), 1997, pp. 151-156
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.