The cytotoxicity of adenosine 5'-[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate in human Tmolt3 leukemic cells.
Adenosine 5'[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate 1 was successfully synthesized and characterized. The compound demonstrated potent in vivo antineoplastic activity and in vitro cytotoxicity in murine and human leukemia and uterine carcinoma tumor cell lines. In human T cell leukemia DNA preferentially was inhibited with key enzymes in the purine pathway being effectively inhibited by the agent. Marginal inhibition of the activities DNA polymerase a, carbamyl phosphate synthetase, nucleoside kinases, and thymidylate synthetase was observed. Tmolt3 DNA strand scission was observed after 24 hr. incubation with compound I at 100 microM.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-73600, USA.
Elkins
A L
AL
Sood
A
A
Tomasz
J
J
Spielvogel
B F
BF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001896:Boron Compounds / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D051379:Mice
D000970:Antineoplastic Agents; D001896:Boron Compounds; C104941:adenosine 5'-(N,N-di-(3-o-carboranyl)propyl)phosphorodiamidate; D004247:DNA; D000241:Adenosine