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.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Elkins
A
A
Powell
W J
WJ
Karthikeyan
S
S
Sood
A
A
Spielvogel
B F
BF
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects*; D015195:Drug Design; D005910:Glioma; D006367:HeLa Cells; D006801:Humans; D007624:KB Cells; D007938:Leukemia; D007939:Leukemia L1210; D015458:Leukemia, T-Cell / Q000378:metabolism; D008175:Lung Neoplasms; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D012516:Osteosarcoma; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001896:Boron Compounds