Synthesis and cytotoxicity of amine-borane adducts of cyclohexylamines and toluidines.
A series of cyano- and carboxyborane adducts of cyclohexylamines and toluidines were shown to be cytotoxic towards suspended single cell tumors. The carboxyborane adducts of cyclohexylamine were more potent than the cyanoborane adducts of cyclohexylamine or any of the toluidine derivatives. A number of the compounds were active at 8 mg/kg/day i.p. in the Ehrlich ascites carcinoma screen in vivo. The mode of action study with N-methylcyclohexylaminecyanoborane 10 in L-1210 lymphoid leukemia cells showed that RNA synthesis was markedly reduced followed by DNA synthesis. Purine de novo synthesis was suppressed at PRPP-amido transferase, IMP dehydrogenase, and dihydrofolate reductase enzyme sites. The agent also interfered with DNA template activity causing reduction of DNA polymerase alpha, and RNA polymerase I, II and III activities. The d[NTP] pools were marginally reduced while DNA viscosity was reduced and DNA fragmentation occurred.
Burnham
B S
BS
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, USA.
Chen
S Y
SY
Sood
A
A
Spielvogel
B F
BF
Hall
I H
IH
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001880:Boranes / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D014052:Toluidines / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001880:Boranes; D003514:Cyclohexylamines; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D014052:Toluidines