Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N2-Isobutyryl-2'-deoxyguanosine-N7-cyanoborane derivatives were observed to be potent antineoplastic agents and to be active against a number of human tissue culture tumor cells, e.g. Tmolt3 leukemia, HeLa-S3 uterine carcinoma. Selective agents were active against colon adenocarcinoma, osteosarcoma and glioma growth. These agents preferentially inhibited both DNA and RNA synthesis of L1210 cells. De novo synthesis of purines was significantly inhibited at the regulatory sites of PRPP amido transferase and IMP dehydrogenase. Other sites of inhibition were thymidylate synthetase, OMP decarboxylase and thymidine kinases. The agents also significantly reduced deoxyribonucleotide levels and caused DNA strand scission.
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PMID:The synthesis and anti-neoplastic activity of N2-isobutyryl-2'-deoxyguanosine-N7-cyanoborane derivatives. 149 12

The sugar boronated thymidine nucleoside, 5' -0-[(triphenylphosphine-boryl) carbonyl]-3'-0-acetyl thymidine 1, and the boron-modified nucleoside phosphotriester, 5'-(diethylphosphite- cyanoborane)-3'-acetylthymidine 2, were successfully synthesized. Both compounds demonstrated differential activity when tested against eight cell lines, with significant cytotoxic activity against the growth of human Tmolt3 leukemia, colon adenocarcinoma, HeLa S3 uterine carcinoma, and osteosarcoma cells. In in vivo studies these agents were found to be active against the growth of Ehrlich ascites carcinoma at 8 mg/kg/day I.P. and to be marginally active against the growth of L1210 and Lewis lung cancers in mice. The mode of action of these thymidine derivatives in Tmolt3 cells was the inhibition of DNA and protein synthesis. Compound 2 was highly effective in inhibiting DNA polymerase alpha and m-RNA, r-RNA and t-RNA polymerase activities. Both compounds inhibited ribonucleoside reductase activity. The de novo purine pathway appeared to be the major site of inhibition of the agents, with IMP dehydrogenase, PRPP amido transferase, and dihydrofolate reductase activities being significantly inhibited. In the pyrimidine pathway, carbamyl phosphate synthetase and aspartate transcarbamylase activities were inhibited by 1. As expected, d[NTP] levels were significantly reduced by treatment with the agents. DNA strand scission was evident after incubating Tmolt3 cells for 24 hr with the agents.
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PMID:Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells. 150 1

Benzohydroxamic acids proved to be potent cytotoxic agents suppressing the growth of a number of murine and human cell lines grown in tissue culture, e.g. leukemia, colon, uterine and glioma. Selected compounds demonstrated activity against the growth KB nasopharynx, bronchogenic lung, osteosarcoma and skin cancer. In vivo activity against Ehrlich ascites carcinoma growth was shown with certain compounds. In L1210 cells compound 2 inhibited DNA synthesis significantly within 60 min. the site of action of the agent appears to involve the purine de novo synthesis pathway at PRPP amido transferase and IMP dehydrogenase. Dihydrofolate reductase and nucleoside kinase activities were inhibited by the agent. The levels of d(NTP)s in L1210 cells were reduced after drug treatment. The drug did not appear to affect the DNA template directly causing any damage which might alter transcription and replication nor was there any inhibition of HeLa topoisomerase activity by the drug. Thus the drug appears to be a metabolic inhibitor of nucleoside metabolism.
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PMID:The antineoplastic and cytotoxicity of benzohydroxamic acids and related derivatives in murine and human tumor cells. 152 9

2,3-Dihydrophthalazine-1,4-dione derivatives demonstrated potent cytotoxicity against the growth of murine leukemia cells and human single cell suspension, i.e. Tmolt3 leukemia and HeLa-S3, as well as colon adenocarcinoma and KB nasopharynx. However, only select compounds demonstrated activity against bronchogenic lung, osteosarcoma and glioma growth. 2,3-Dihydrophthalazine-1,4-dione was active in vivo against L1210 leukemia, Lewis lung and Ehrlich ascites carcinoma growth. In L1210 cells the agents inhibited both DNA and RNA synthesis, and a few of the compounds were capable of inhibiting protein synthesis at 3 times their ED50 values. When 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione were examined for their mode of action in the L1210 lymphoid leukemia cells, the sites of inhibition by the agents appear to be the de novo purine pathway at the enzymes IMP dehydrogenase and PRPP amido transferase. IMP dehydrogenase activity was inhibited at least 45% by 45 min at 100 microM concentration of drugs whereas the remaining enzymes that were affected by the drugs were not inhibited as early. Secondary sites were dihydrofolate reductase and thymidylate synthetase. The d(NTP) levels were also reduced specifically dATP and dCTP levels.
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PMID:The anti-neoplastic activity of 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione in human and murine tumor cells. 162 17

Boron analogues of piperidine, piperazine, morpholine, and imidazole proved to be cytotoxic against the growth of murine and human tissue culture cells. Significant activity was demonstrated for single-cell suspensions of L1210 lymphoid leukemia, Tmolt3 lymphoblastic leukemia, and HeLa-S3 cervical carcinoma. Trimethylamine-imidazole carbonyldihydroborane 17 demonstrated activity against solid tumor growth of human colorectal adenocarcinoma, KB nasopharynx, and osteosarcoma. In addition, 4-methylpiperidine-carbomethoxyborane 12, 2-methylimidazole-3-cyanoborane 16, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were active against the KB nasopharynx growth. Piperidine-cyanoborane 2, piperidine-carboxyborane 4, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were effective in reducing the growth of osteosarcoma cells. The imidazole derivatives 13-19, as well as 4-methylpiperidine-carboxyborane 11 and carbomethoxyborane 12, demonstrated good activity against lung bronchogenic and glioma growth. In the in vivo studies, N-methylmorpholine-carboxyborane 7,4-phenylpiperidine-carboxyborane 9, 4-phenylpiperidine-carbomethoxyborane 10, 4-methylpiperidine-carboxyborane 11, imidazole cyanoborane 14, and 1-methylimidazole-3-carbomethoxyborane 18 demonstrated the best activity against Lewis Lung growth and P388 lymphocytic leukemia growth in mice. Mode of action studies in L1210 leukemia cells demonstrated that piperidine-carboxyborane 4 and N-methylmorpholine-carboxyborane 7 inhibited DNA synthesis, purine synthesis at PRPP amido transferase and IMP dehydrogenase sites, and thymidine kinase and thymidine diphosphate kinase activities, while lowering d(NTP) pool levels. Also, DNA strand scission was evident after incubation with these drugs.
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PMID:Synthesis and antineoplastic activity of some cyano-, carboxy-, carbomethoxy-, and carbamoylborane adducts of heterocyclic amines. 181 71

Substituted oxoisoindolines are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. In general these agents were not active against the solid cell growth, i.e. KB, skin, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. Purine synthesis was reduced by compound 16 at both regulatory enzymes, i.e. PRPP amido transferase, IMP dehydrogenase and dihydrofolate reductase. The agent lowered d(GTP) and d(CTP) pool levels, further reducing DNA synthesis. DNA strand scission was evident after incubation with Compound 16 for 24 hr at 100 microM and some undefined interaction between the drug and the nucleoside bases appeared to occur, lowering DNA synthesis and causing cell death.
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PMID:The cytotoxicity of [(N-alkyl-1H,3H-1-oxoisoindoline-5-yl-oxyl alkanoates and related benzamides in murine and human tissue cultured cell lines. 765 21

Substituted isoindoline-1,3-diones are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. In general these agents were not active against the solid cell growth, i.e. KB, skin, colon, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. Purine synthesis was reduced by compound 4 at both regulatory enzymes, i.e. PRPP amido transferase and IMP dehydrogenase. The agent lowered d(GTP) pools, further reducing DNA synthesis. DNA strand scission was evident after incubation with Compound 4 for 24 hr at 100 microM, lowering DNA synthesis and causing cell death.
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PMID:The cytotoxicity of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]-alkanoic acids in murine and human tissue cultured cell lines. 765 22

N-Substituted indan-1.3-diones have proven to be potent cytotoxic agents effective against the growth of single cell leukemia tumors and cell lines derived from solid tumors. A number of the derivatives were active against growth of solid tumors e.g. colon, lung bronchogenic and osteosarcoma for which few effective agents are available to inhibit their growth. These agents inhibited DNA and RNA synthesis of L1210 cells. The de novo purine synthetic pathway was inhibited at PRPP amido transferase and IMP dehydrogenase. The pyrimidine synthetic pathway was inhibited at aspartate transcarbamylase. Other sites which demonstrate minor inhibition were DNA polymerase alpha, r- and t-RNA polymerase, ribonucleoside reductase, dihydrofolate reductase, nucleoside kinases and thymidylate synthetase. In addition d(NTP) pool levels were reduced by the drugs. L1210 DNA strand scission was evident after exposure to drugs for 24 hr. at 100 microM.
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PMID:Cytotoxicity and mode of action of substituted indan-1, 3-diones in murine and human tissue cultured cells. 784 49

Certain types of hypolipidemic agents have been observed to also function as cytotoxic agents. Previously reported hypolipidemic agents, 3-imino-1-oxoisoindolines, were evaluated for their anti-neoplastic activity. Selected agents were effective at inhibiting L1210, Tmolt3, HeLa-S3, KB nasopharynx, lung, osteosarcoma and glioma growth. 2-Propyl-3-imino-1-oxoisoindoline, (4), a representative compound of the class of agents, inhibited DNA and RNA syntheses of L1210 cells. The major site of inhibition was the purine pathway at IMP dehydrogenase. Other enzyme sites which were affected by (4) marginally were t-RNA and r-RNA polymerases, dihydrofolate reductase, aspartate transcarboxylase, and nucleoside kinases. d(NTP) pools of L1210 cells were reduced after 60 min. Incubation with (4).
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PMID:The cytotoxicity of 3-imino-1-oxoisoindolines in murine and human tissue culture cells. 804 4

Heterocyclic thiosemicarbazones, thioureas and 2-substituted pyridine N-oxides as well as representative nickel, cobalt and copper complexes were shown to be potent antineoplastic/cytotoxic agents. The cytotoxicity was demonstrated against single cell leukemia as well as cell lines derived from solid tissue (colon adenocarcinoma, HeLa, KB, skin, bronchogenic lung, bone osteosarcoma and glioma). In L1210 cells, DNA synthesis and subsequently RNA synthesis were particularly inhibited by the agents. IMP dehydrogenase activity and thus purine de novo synthesis was reduced significantly by the agents. Dihydrofolate reductase, ribonucleoside reductase, nucleoside kinase and DNA polymerase alpha activities were inhibited by the agents. d(NTP) pool levels were reduced by most of the agents. DNA strand scission was present with all of the derivatives; however, there was no evidence of intercalation, cross linking or alkylation/binding to bases of DNA. This new group of compounds may offer novel exploratory derivatives for future investigations in the treatment of cancer.
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PMID:The cytotoxicity of heterocyclic thiosemicarbazones and their metal complexes on human and murine tissue culture cells. 849 Feb 2


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