Biomedical subjects

B F Spielvogel

Publications and source records attributed to B F Spielvogel.

40 records · Page 3Linked to original sources

PubMedDate not supplied

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.

Adenosine↗

PubMedDate not supplied

The cytotoxicity of 1-(phenylmethyl)-4,7,10-tris-[(4'methylphenyl) sulfonyl]-1,4,7,10-tetraazacyclododecane in human Tmolt3 T leukemic cells.

1-(phenylmethyl)-4,7,10-tris-[(4'methylphenyl)-sulfonyl]-1,4,7, 10-tetraazacyclododecane proved to possess potent in vivo antineoplastic and in vitro cytotoxicity in murine and human tissue cultured cells. In Tmolt3 leukemic cells 1-(phenylmethyl)-4,7,10-tris-[(4'methylphenyl)sulfonyl]-1,4,7, 10-tetraazacyclododecane inhibited the activities of the regulatory enzymes of the purine pathway leading to significant reductions in both RNA and DNA synthesis. Other sites of action of the compound which led to reductions of nucleic acid synthesis were suppression of nucleoside kinase and thymidylate synthetase activities and reductions in the d[NTP] pool levels. DNA fragmentation occurred which should be linked directly with cancer cell death.

Antineoplastic Agents↗

PubMedDate not supplied

Synthesis and antitumor activity of boronated dipeptides containing aromatic amino acids.

N-[(Trimethylamine-boryl-carbonyl]-L-tryptophan methyl ester and N[(trimethylamine-boryl)-carbonyl]-L-histidine methyl ester were obtained by synthesis using triphenyl-phosphine/carbon tetrachloride or dicyclohexyl-carbodiimide as coupling agents, respectively. Both agents reduced L1210 lymphoid leukemia DNA, RNA, and protein syntheses with the largest reductions occurring in DNA synthesis. Reductions in DNA synthesis appear to be mediated by inhibition of key enzyme activities (i.e., DNA polymerase a, IMP dehydrogenase, and PRPP amido transferase). These agents had little effect on in vitro L1210 DNA topoisomerase II activity at 100 microM but were able to cause synergistic increases in protein-linked DNA breaks when combined with etoposide (VP16). It was shown that these agents significantly reduced protein kinase C mediated phosphorylation of human topoisomerase II in vitro. Thus, inhibition of topoisomerase II phosphorylation may be a mechanism by which these agents and VP-16 are synergistic in causing protein-linked DNA breaks.

Animals↗

PubMedDate not supplied

Substituted carboranes and polyhedral hydroborate salts as anti-neoplastics.

Substituted carboranes and polyhedral hydroborate salts were observed to be potent anti-neoplastic/cytotoxic agents inhibiting the growth of mouse and human leukemias, human uterine, colon adenocarcinoma, lung bronchogenic and gliomas. Amino-o-carborane-hydrochloride 7, one of the more potent compounds, preferentially inhibited Tmolt3 DNA synthesis. The target of the agent appears to be de novo purine synthesis with significant inhibition of the activities of both regulatory enzymes, PRPP-amido transferase and inosine monophosphate dehydrogenase as well as dihydrofolate reductase. The agent also inhibited nucleoside kinase activities leading to reductions in deoxyribonucleotide pools. The DNA molecule itself was not a target of the agent.

Adenocarcinoma↗