Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A series of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes and cyanoboranes were synthesized. These compounds have potent hypolipidemic effects, antineoplastic and antiinflammatory activities in rodents. Furthermore, they demonstrated potent cyctotoxicity against standard human tissue culture lines. The compounds which afforded the best hypolipidemic activity, i.e. greater than 40% reduction of serum cholesterol and triglyceride levels, were diphenyl-(4-methylphenyl)-phosphine borane and triphenylphosphine carboxyborane. Other derivatives demonstrated more potent antineoplastic activity against the Ehrlich ascites carcinoma growth including triphenylphosphine cyanoborane, 2-amino-4-methyl-pyridine cyanoborane and 2-amino-pyridine cyanoborane. Most of the derivatives showed good activity against murine L1210 lymphoid leukemia, Tmolt3 human leukemia, uterine HeLaS cells, and human glioma cell growth. Select compounds were active against colon adenocarcinoma, KB nasopharynx, lung bronchogenic and osteosarcoma cell growth. Tricyclohexyl- and triphenylphosphine boranes and the carboxy derivatives of the latter borane demonstrated good antiinflammatory activity.
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PMID:Relationship of hypolipidemic and antineoplastic activities of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes, cyanoboranes, and related derivatives. 152 68

Naturally occurring sesquiterpene lactones and their semisynthetic derivatives, such as the O = C-C = CH-bearing helenalin and its esters, have been shown to demonstrate potent cytotoxicity against the growth of murine L1210 lymphoid leukemia and human Tmolt3 leukemia, colon adenocarcinoma, HeLaS3, lung bronchogenic, KB, osteosarcoma, and glioma cells. The modes of action of helenalin in L1210 cells are the inhibition of DNA, RNA, and protein syntheses. This study confirms that thiol bearing enzymes of nucleic acid metabolism were significantly inhibited, e.g. DNA polymerase alpha, IMP hydrogenase, and ribonucleoside reductase. The addition of GSH to the reaction medium demonstrated total recovery of L1210 ribonucleoside reductase activity. Helenalin reduced cellular GSH levels in L1210 cells. Helenalin also reduced all four pool levels of d(NTP)s which would account for part of the observed inhibition of DNA synthesis. Reductions in the ribonucleotide pool levels were also generally evident after drug treatment. Thus, the sesquiterpene lactones appear to have more than one mode of action in L1210 cells. All of the modes of actions of helenalin are feasible mechanisms to lower nucleic acid synthesis and cause cell death of the L1210 leukemia cells.
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PMID:The cytotoxicity of helenalin, its mono and difunctional esters, and related sesquiterpene lactones in murine and human tumor cells. 152 2

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

The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life span of mice bearing P388 leukemia. CNDAC had a unique in vitro antitumor spectrum for human cancers different from that of ara-C. Compared with ara-C, CNDAC was more effective in 10 human tumors (2 lung, 4 stomach and 4 osteosarcoma), equal in 2 tumors (lung and fibrosarcoma) and less potent in 11 tumors (4 lung, 4 osteosarcoma, bladder, renal and epidermoid). Characteristically CNDAC showed excellent activities against tumors, refractory to ara-C, such as HT-1080 human fibrosarcoma implanted in chick embryos or athymic mice, although its cytotoxicity against HT-1080 was almost equal to that of ara-C. Thus, CNDAC is an interesting and promising agent that should be considered for further detailed preclinical evaluation.
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PMID:Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) against murine and human tumors. 159 80

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

Acute nonlymphocytic leukemia (ANLL) developed in 2 of 142 pediatric patients with osteosarcoma treated with a cis-diamminedichloroplatinum-II (CDP)-based regimen: acute monomyelogenous leukemia (M4) with a normal female karyotype in one and acute myelogenous leukemia (M2) with t (8,21) in the other. The ANLLs occurred, respectively, in each patient 3 and 4 years after the initial diagnosis of osteosarcoma. In contrast to most of the adult experience and consistent with the majority of reported ANLL in children, the disease was characterized by an absence of the smoldering phase and cytogenetic findings similar to those seen in de novo ANLL.
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PMID:Secondary acute non-lymphoblastic leukemia in two children following treatment with a cis-diamminedichloroplatinum-II-based regimen for osteosarcoma. 172 15

We isolated four monoclonal antibodies (MAbs), M38, M101, M104, and C33, which were capable of inhibiting syncytium formation induced in a human T-cell line, MOLT-4-#8, by coculture with human T-cell leukemia virus type 1 (HTLV-1)-positive human T-cell lines. The MAbs had, however, no inhibitory activity on syncytium formation induced in a human osteosarcoma line, HOS, by HTLV-1-positive T-cell lines. They also did not inhibit syncytium formation induced in MOLT-4-#8 by human immunodeficiency virus type 1-positive MOLT-4. All MAbs reacted with various human cell lines of lymphoid and nonlymphoid origins, including HTLV-1-positive T-cell lines. Furthermore, they all reacted with a murine A9 clone containing human chromosome 11 fragment q23-pter. Two MAbs, M104 and C33, immunoprecipitated a membrane antigen with the same molecular size. The antigen (henceforth called C33 antigen) was about 40 to 55 kDa in HTLV-1-negative Jurkat, CEM, MOLT-4, and normal peripheral blood CD4-positive human T cells and about 40 to 75 kDa in HTLV-1-positive C91/PL, TCL-Kan, MT-2, and in fresh HTLV-1-transformed CD4-positive human T-cell lines. Pulse-chase experiments revealed that C33 antigen was synthesized as a 35-kDa precursor that was then processed to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL. In the presence of tunicamycin, a 28-kDa protein was synthesized. The conversion from 35 kDa to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL was inhibited by monensin. Treatment with N-glycanase alone, but not with sialidase and O-glycanase in combination, completely removed the sugar moiety of C33 antigen from both HTLV-1-negative Jurkat and HTLV-1-positive C91/PL. Therefore, C33 antigen has only N-linked carbohydrates, the modification of which appears to be substantially altered in the presence of the HTLV-1 genome.
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PMID:Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells. 173 99

Flavonolignans isolated from Hydnocarpus wightiana seeds, namely hydnowightin, hydnocarpin, and neohydnocarpin, demonstrated potent hypolipidemic activity in mice, lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day ip. Hydnowightin demonstrated the best lipid-lowering effect of the three compounds. Good anti-inflammatory and antineoplastic activity was demonstrated by hydnocarpin in mice in vivo. The other two derivatives were not as active in these screens. Cytotoxicity against the growth of murine and human tissue cultured cells was shown. All three compounds were moderately active against murine L-1210 leukemia growth. All three compounds demonstrated good activity against the growth of human KB nasopharynx, colon adenocarcinoma, osteosarcoma, and HeLa-S3 uterine growth. Hydnocarpin was the only compound of the three which was active against glioma growth. Hydnocarpin and neohydnocarpin demonstrated significant activity against Tmolt3 leukemia cell growth.
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PMID:Hypolipidemic, anti-inflammatory, and antineoplastic activity and cytotoxicity of flavonolignans isolated from Hydnocarpus wightiana seeds. 180 Jun 32

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


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