DNA interaction with metal complexes and salts of substituted boranes and hydroborates in murine and human tumor cell lines.
A series of metal complexes and sodium salts of substituted boranes and hydroborates was shown to have cytotoxicity in murine and human tumor screens. Most of these agents were active against the growth of L-1210, Tmolt3 and Hela-S3. Selected agents demonstrated activity against the growth of monolayer human cell lines derived from solid tumors. Interestingly, many of the compounds demonstrated even lower ED50 values in the solid tumor than the L-1210 leukemic screen. Four compounds, Cu2(m-CH3)3NBH2CO2)4.2(CH3)NBH2COOH (I), [Fe3O((CH3)3NBH2CO2)6(CH3OH)3]NO3.CH3CN (II), cis-[Co(en)2((CH3)3N.BH2CO2)2]Cl.2.5 H2O.0.5 CH3OH (V), and Na(CH3)3NBH2CO2.0.25 CH3OH (IX) were shown preferentially to inhibit DNA synthesis of L-1210 cells with only moderate inhibition of RNA and protein synthesis. In preliminary studies these agents effectively inhibited the activities of regulatory enzymes involved in the purine pathway and nucleoside kinases resulting in the suppression of d(NTP) pool levels. The boron derivatives also caused L-1210 DNA strand scission. These drugs may act together to inhibit DNA synthesis and induce cytotoxicity.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Morse
K W
KW
Spielvogel
B F
BF
Sood
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001880:Boranes / Q000737:chemistry* / Q000494:pharmacology; D001881:Borates / Q000737:chemistry* / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry*; D007939:Leukemia L1210 / Q000188:drug therapy; D008670:Metals / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001880:Boranes; D001881:Borates; D001896:Boron Compounds; D004273:DNA, Neoplasm; D008670:Metals; D009363:Neoplasm Proteins