The synthesis and antitumor activity of metal complexes of amine-carboxyborane adducts

The amine carboxyborane metal complexes, tetrakis - μ - (trimethylamine - boranecarboxylato)acetonitrile dicopper(II) and his-μ-(morpholine-boranecarboxylato)zinc(II) dihydrate demonstrated cytotoxic activity against human Tmolt 3 , HeLa-S 3 and MB-9812 cell growth. Tetrakis-μ-(trimethylamine-boranecarboxylato)-acetonitrile dicopper(II) and bis - μ - (morpholine - boranecarboxylato)zinc (II) dihydrate inhibited L 1210 DNA, RNA and protein syntheses, with greatest inhibitory effects on DNA synthesis. The reduction in DNA synthesis correlates well with inhibition of de novo purine synthesis and the key enzymes involved in this pathway, i.e. IMP dehydrogenase and PRPP amido transferase. These compounds were also observed to induce DNA strand scission but did not appear to intercalate between base pairs of DNA, alkylate bases or cause cross-linking of the strands of DNA. Tetrakis-μ-(trimethylamine - boranecarboxylato)acetonitrile dicopper(II) also demonstrated the ability to inhibit L 1210 DNA topoisomerase II activity.

[1]  M. Waring,et al.  Salen-anthraquinone conjugates. Synthesis, DNA-binding and cleaving properties, effects on topoisomerases and cytotoxicity. , 1996, Bioorganic & medicinal chemistry.

[2]  C. Lin,et al.  Modification of DNA topoisomerase I enzymatic activity with phosphotyrosyl protein phosphatase and alkaline phosphatase from the hepatopancreas of the shrimp Penaeus japonicus (Crustacea:Decapoda). , 1996, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[3]  C. K. Sood,et al.  Synthesis, cytotoxicity, hypolipidemic and anti-inflammatory activities of amine-boranes and esters of boron analogues of choline and thiocholine. , 1992, Journal of pharmaceutical sciences.

[4]  C. K. Sood,et al.  Synthesis and antineoplastic activity of some cyano-, carboxy-, carbomethoxy-, and carbamoylborane adducts of heterocyclic amines. , 1991, Journal of pharmaceutical sciences.

[5]  K. Morse,et al.  DNA interaction with metal complexes and salts of substituted boranes and hydroborates in murine and human tumor cell lines. , 1991, Anti-cancer drugs.

[6]  I. Hall,et al.  The antineoplastic activity of trimethylamine carboxyboranes and related esters and amides in murine and human tumor cell lines. , 1990, Anti-cancer drugs.

[7]  G. Hofmann,et al.  Quantitative adaptation of the bacteriophage P4 DNA unknotting assay for use in the biochemical and pharmacological characterization of topoisomerase II. , 1990, Anti-Cancer Drug Design.

[8]  K. Lee,et al.  Antimalarial agents. III. Mechanism of action of artesunate against Plasmodium berghei infection. , 1987, Chemical & pharmaceutical bulletin.

[9]  K. Morse,et al.  Synthesis and characterization of cobalt(III), cobalt(II), zinc(II), and calcium(II) complexes containing the trimethylamine-boranecarboxylato ligand (CH3)3N.cntdot.BH2COO- , 1987 .

[10]  K. Morse,et al.  Metal complexes containing the trimethylamine-carboxylatoborane ligand: synthesis and characterization of [M3O((CH3)3N.BH2CO2)6R3]+X- (M = Cr(III), Fe(III); R = H2O, CH3OH; X- = NO3-, Cl-) , 1986 .

[11]  T. Beerman,et al.  Induction of deoxyribonucleic acid damage in HeLa S3 cells by cytotoxic and antitumor sesquiterpene lactones. , 1981, Biochemical pharmacology.

[12]  C. Rawlings,et al.  Quantitative aspects of the formation and loss of DNA interstrand crosslinks in Chinese hamster cells following treatment with cis-diamminedichloroplatinum(II) (cisplatin). II. Comparison of results from alkaline elution, DNA renaturation and DNA sedimentation studies. , 1981, Biochimica et biophysica acta.

[13]  L. Liu,et al.  A homogeneous type II DNA topoisomerase from HeLa cell nuclei. , 1981, The Journal of biological chemistry.

[14]  D. Hunting,et al.  Determination of deoxyribonucleoside triphosphates using DNA polymerase: a critical evaluation. , 1981, Canadian journal of biochemistry.

[15]  L. Liu,et al.  Novel topologically knotted DNA from bacteriophage P4 capsids: studies with DNA topoisomerases. , 1981, Nucleic acids research.

[16]  R. Christopherson,et al.  An overall radioassay for the first three reactions of de novo pyrimidine biosynthesis. , 1981, Analytical biochemistry.

[17]  N. Tanaka,et al.  Mechanism of action of macromomycin: DNA strand scission, inhibition of DNA synthesis and mitosis. , 1978, The Journal of antibiotics.

[18]  D. Eichler,et al.  Effect of calcium on the recovery and distribution of DNA polymerase alpha from cultured human cells. , 1977, The Journal of biological chemistry.

[19]  A. Leibovitz,et al.  Classification of human colorectal adenocarcinoma cell lines. , 1976, Cancer research.

[20]  S. Osaki,et al.  Synthetic inhibitors of Escherichia coli, calf thymus, and Ehrlich ascites tumor thymidylate synthetase. , 1976, Journal of medicinal chemistry.

[21]  G. Russev,et al.  Some pyrazoles as inhibitors of purine biosynthesis de novo. , 1976, Biochemical pharmacology.

[22]  S. Horwitz,et al.  Mode of action of the antitumor compound bruceantin, an inhibitor of protein synthesis. , 1976, Molecular pharmacology.

[23]  K. Anderson,et al.  Solubilized DNA-dependent nuclear RNA polymerases from the mammary glands of late-pregnant rats. , 1975, Biochimica et biophysica acta.

[24]  C. Piantadosi,et al.  Cycloalkanones. 4. Antifertility activity. , 1974, Journal of medicinal chemistry.

[25]  M. Sasada,et al.  Effect of neocarzinostatin on DNA synthesis in L1210 cells. , 1974, Cancer research.

[26]  M. Hakala,et al.  5-(1-Adamantyl) pyrimidines as inhibitors of folate metabolism. , 1972, Cancer research.

[27]  L. R. Finch,et al.  Quantitative extraction and estimation of intracellular nucleoside triphosphates of Escherichia coli. , 1972, Analytical Biochemistry.

[28]  Moore Ec,et al.  Regulation of Mammalian Deoxyribonucleotide Biosynthesis by Nucleotides as Activators and Inhibitors , 1966 .

[29]  T. Brzozowski,et al.  Purification and properties of a bacterial carbamyl phosphate synthetase. , 1966, The Journal of biological chemistry.

[30]  S. Ochoa,et al.  Enzymatic phosphorylation of deoxycytidylic acid. , 1958, The Journal of biological chemistry.

[31]  P. Cohen,et al.  Colorimetric determination of carbamylamino acids and related compounds. , 1954, The Journal of biological chemistry.

[32]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[33]  F. Wilcoxon,et al.  A simplified method of evaluating dose-effect experiments. , 1948, The Journal of pharmacology and experimental therapeutics.

[34]  R. Archibald.  DETERMINATION OF CITRULLINE AND ALLANTOIN AND DEMONSTRATION OF CITRULLINE IN BLOOD PLASMA , 1944 .