The antineoplastic activity of trimethylamine carboxyboranes and related esters and amides in murine and human tumor cell lines.
Trimethylamine carboxyboranes including their esters and amides were shown to have antineoplastic activity in vivo against Ehrlich ascites carcinoma growth. The derivatization to the ester or amide did not necessarily improve activity. Cytotoxicity of the derivatives was observed against the growth of murine and human tumor cells. Selectivity was demonstrated by the boron derivatives in the human solid tumor screens. Almost all the compounds demonstrated cytotoxicity against single-cell suspension growths, eg Tmolt3, L1210, HeLa-S3. Selection of two compounds to examine their mode of action in L1210 lymphoid leukemia cells showed that the agents perferentially inhibited DNA synthesis followed by protein and RNA synthesis. The d(TTP) pools were markedly reduced because of inhibition of nucleotide kinase activity. The agents also inhibited regulatory enzymes in the de novo purine pathway and afforded DNA strand scission. These effects by the agents were probably additive to bring about tumor cell death.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Spielvogel
B F
BF
Sood
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001880:Boranes / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009696:Nucleic Acids / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001880:Boranes; D008744:Methylamines; D009363:Neoplasm Proteins; D009696:Nucleic Acids; C023336:trimethylamine