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

A series of 32 cationic platinum(II) complexes of the form cis-[PtA2(Am)Cl]+, where A is a monodentate (NH3 or i-PrNH2) or A2 is a bidentate (ethylenediamine or 1,2-diaminocyclohexane) amine and Am is either a heterocyclic amine based on a pyridine, pyrimidine, purine, piperidine, or a saturated amine (RNH2) ligand, was prepared and screened against in vivo murine tumor models. Each compound was tested against Sarcoma 180 ascites (S180a) in mice, with 20 members of the series showing activity (ILS greater than 50%). Antitumor activity also was demonstrated in 4 of 16 compounds tested in the L1210 murine leukemia model (ILS greater than 25%) and in 3 of 3 tested in the P388 murine leukemia model (ILS greater than 30%). The most active and potent analogues of the series were obtained when A was NH3 and Am was N1-pyridine, N1-4-methylpyridine, N1-4-bromopyridine, N1-4-chloropyridine, N3-cytosine, or N7-2'-deoxyguanosine. Complexes containing chelating and saturated amine ligands (A), as well as two trans isomers of active cis analogues (trans-[Pt(NH3)2(Am)Cl]+, where Am = N1-pyridine or N1-4-methylpyridine), were inactive in the S180a screen. All complexes were characterized by means of elemental analysis, HPLC, and 195Pt NMR spectroscopy, and the structure of one analogue, cis-[Pt(NH3)2(N3-cytosine)Cl](NO3), was determined by using single-crystal X-ray diffraction methods. While members of this series of compounds demonstrate antitumor activity in vivo, these new agents are not classical analogues of cisplatin (i.e. cis-[PtA2X2] complexes), as they contain three nitrogen donors and only one leaving group. The results of these studies suggest that further work should be conducted to better define the limits of the structure-activity relationships among platinum(II) complexes.
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PMID:Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+. 290 24

On the basis of qualitative structure-activity relationships developed in the preceding article, a series of 32 new mitomycin A analogues were prepared and tested in antitumor screens. Seven of them gave greater prolongation of life (ILS) than mitomycin C in the mouse P388 leukemia assay. They included examples with 7-O substituents such as cyclic ethers and nitrogen heterocycles. A Hansch analysis was attempted with log P and MR as the independent variables, but no statistically significant correlation could be made. Seven compounds, chosen mainly for their good potency (MED), were tested in the subcutaneous B16 melanoma assay in mice and four of them showed greater ILS than mitomycin C.
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PMID:Preparation and antitumor activity of additional mitomycin A analogues. 291 19

The antitumor effects of three 5-fluorouracil-related compounds, 5'-deoxy-5-fluorouridine (5'-DFUR), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-fluorouracil (5-FU) itself, on several experimental murine tumors were compared after oral administration. 5'-DFUR showed strong antitumor activity against the solid type of four kinds of tumors tested with a wide range of effective doses, and also showed moderate antitumor activity against three kinds of solid tumors with a narrow range of effective doses. 5'-DFUR was effective against a few kinds of ascites tumors. In general, the antitumor activity of FT-207 was not very strong, with narrow ranges of effective doses under the present conditions. 5-FU showed strong toxicity but at lower doses its antitumor effectiveness was almost the same as that of FT-207. When the doses were divided into three and the divided dose was given orally three times a day for five consecutive days to mice bearing L1210 leukemia, this modality (with any of the three drugs) enhanced the ILS of the mice by two to three times in the case of the ascites type but not the solid type of L1210. The chemotherapeutic index in oral treatment of the solid type of tumors was higher for 5'-DFUR than for FT-207 or 5-FU. The minimum lethal doses in oral administration for five consecutive days were about 3, 1.5 and 0.5 mmol/kg/day for 5'-DFUR, FT-207 and 5-FU, respectively. In conclusion, 5'-DFUR appeared to have stronger antitumor activity and less toxicity than FT-207 and 5-FU, and it is therefore expected to be clinically useful.
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PMID:The therapeutic effects of orally administered 5'-deoxy-5-fluorouridine, 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil on experimental murine tumors. 293 56

The effects of Ara-C derivatives, 5-FU derivatives and water-soluble nitrosoureas on L1210 leukemia implanted intracerebrally have been evaluated. Daily treatment with BH-AC showed a similar effect to that of Ara-C and intermittent treatment with BH-AC showed a marked effect. Daily treatment with FT-207, UFT and HCFU, 5-FU derivatives, resulted in more than 50% ILS but the effects of these compounds were inferior to those of ACNU and BH-AC. MCNU, a water-soluble nitrosourea, was effective, but less so than ACNU.
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PMID:[Effects of derivatives of Ara-C, 5-fluorouracil and nitrosourea against intracerebral implanted L1210 leukemia]. 294 3

Azinomycins A and B, isolated from the culture broth of Streptomyces griseofuscus S 42227, were examined for antitumor activities against P388 leukemia, P815 mastocytoma, B-16 melanoma, Ehrlich carcinoma, Lewis lung carcinoma and Meth A fibrosarcoma. Azinomycin B was markedly effective against the intraperitoneally inoculated tumors such as P388 leukemia, B-16 melanoma and Ehrlich carcinoma. The intraperitoneal administration of azinomycin B showed 57% survivors for 45 days and 193% ILS against P388 leukemia. For Ehrlich carcinoma, azinomycin B gave 161% ILS and 63% survivors for 45 days, but solid tumors such as Lewis lung carcinoma and Meth A fibrosarcoma were not susceptible to repeated injection of this substance. Azinomycin A was somewhat less effective than azinomycin B for the tumor systems tested.
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PMID:Azinomycins A and B, new antitumor antibiotics. III. Antitumor activity. 310 67

This report describes a structure-activity analysis of isomers of three classes of dihydroxybenzene derivatives, including dihydroxybenzaldoxime, dihydroxybenzaldehyde, and dihydroxybenzonitrile. These derivatives were examined for their effect on ribonucleotide reductase activity, macromolecular synthesis, cell growth, and in vivo antitumor activity against the L1210 murine leukemia. One of the compounds studied exhibited significant antitumor activity against the growth of L1210 leukemia cells. A comparison of the various analogues revealed a possible correlation for 3,4-dihydroxybenzaldoxime between its potent inhibitory effect toward ribonucleotide reductase activity (IC50 = 38 microM) and its superior L1210 antitumor activity [percent increased life span (% ILS) = 100].
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PMID:Antitumor effects of biologic reducing agents related to 3,4-dihydroxybenzylamine: dihydroxybenzaldehyde, dihydroxybenzaldoxime, and dihydroxybenzonitrile. 331 71

Antileukemic activity of pretazettine hydrochloride (PTZ: a narcissus alkaloid) and Viva-Natural (a seaweed extract) has been confirmed against spontaneous AKR T cell leukemia in mice containing 20% of advanced leukemia. The activity of both agents has been compared with selected standard cytotoxic drugs, vincristine (VCR), methotrexate (MTX), 6-thioguanine (6-TG), and adriamycin (ADR), and immunomodulators, pyran copolymer (MVE-2), isoprinosine, levamisole and tilorone. PTZ activity seems to be superior (90% increase in life span, ILS) to those of MTX (71% ILS), 6-TG (60%), and ADR (49%), and inferior to VCR (114% ILS). Viva-Natural has been found to be the only immunomodulator (61%) active against AKR T cell leukemia, while all standard immunomodulators tested were not active. Combination treatment of PTZ with VCR, or 6-TG, or ADR, or Viva-Natural were synergistic, but combination of PTZ with MTX was not beneficial. PTZ or VCR has been found to be therapeutically very effective (323 or 347% ILS, respectively) against mice in advanced stage of leukemia, and induced complete clinical remissions. Also, PTZ has been found to reverse the leukemia-enhancing effect of ciclosporin in AKR mice at preleukemic stage.
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PMID:Effect of pretazettine and viva-natural, a dietary seaweed extract, on spontaneous AKR leukemia in comparison with standard drugs. 336 94

The antitumor activity of RA-700, a cyclic hexapeptide isolated from Rubia Cordifolia, was evaluated in comparison with deoxy-bouvardin and vincristine (VCR). As regards the proliferation of L1210 cultured cells, the cytotoxicity of RA-700 was similar to that of VCR but superior to that of deoxy-bouvardin. The IC50 value of RA-700 was 0.05 mcg/ml under our experimental conditions. RA-700 inhibited the incorporation of 14C-leucine at a concentration at which no effects were observed on the incorporation of 3H-thymidine and 3H-uridine in L1210 culture cells in vitro. The antitumor activity of RA-700 was similar to that of deoxy-bouvardin and VCR against P388 leukemia. Daily treatment with RA-700 at an optimal dose resulted in 118% ILS. As with deoxy-bouvardin and VCR, the therapeutic efficacy of RA-700 depends on the time schedule. RA-700 showed marginal activity against L1210 leukemia (50% ILS), similar to that of deoxy-bouvardin but inferior to that of VCR. RA-700 inhibited Lewis tumor growth in the early stage after tumor implantation, whereas deoxy-bouvardin and VCR did not. As regards toxicity, a slight reduction of peripheral WBC counts was observed with the drug, but no reduction of RBC and platelet counts. BUN, creatinine, GPT and GOT levels in plasma did not change with the administration of the drug.
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PMID:Antitumor activity and toxicity in mice of RA-700, a cyclic hexapeptide. 363 86

Three 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of 1-S-alkyl-phospholipids (thioether phospholipids) were tested for their antitumor efficacies against L1210 and P388 leukemia in mice. These include 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-rac-1-S-hexadecyl-2-0-palmitoyl-1-thioglycerol (ara-CDP-beta-palmitoyl-DL-thiochimyl alcohol, I), ara-CDP-rac-1-S-octadecyl-2-0-palmitoyl-1-thioglycerol (ara-CDP-beta-palmitoyl-DL-thiobatyl alcohol, II), and ara-CDP-rac-1-S-octadecyl-2-0-hexadecyl-1-thioglycerol (ara-CDP-beta-cetyl-DL-thiobatyl alcohol, III). Conjugates I and II produced significant increase in life span (293-379%) and longterm survivors among mice bearing i.p. implanted L1210 lymphoid leukemia at a total dose of 400 mg (389-400 mumol)/kg. Conjugate II also displayed a strong antitumor activity against i.c. implanted L1210 leukemia in mice with an ILS range of 160-200% at a total dose of 300-450 mg (292-438 mumol/kg. Significant schedule dependency was not observed when the conjugates were administered i.p. once daily with following schedules: qd l; 1,5, 9; 1-5; and 1-9, but single doses typically produced the best effects. The i.p. administration of conjugate II gave the best results on survival of i.p. inoculated L1210 leukemic mice, then followed by the s.c. and i.m. treatments. The i.v. treatment produced a lower activity than the others. Conjugate II also exhibited a strong antitumor activity against i.p. implanted P388 leukemia in mice with ILS values of greater than 255-greater than 329% with 3-5 45-day survivors at a total dose of 300-500 mg (292-486 mumol)/kg (qd 1 or 1-5). The new conjugates I and II displayed a comparable or somewhat higher activity than the previous diacyl and 1-0-alkyl analogs.
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PMID:1-beta-D-arabinofuranosylcytosine conjugates of thioether phospholipids as a new class of potential antitumor drugs. 370 34

The effect of thymidine (dThd) on 5-fluorouracil (FUra) toxicity to both leukemia stem cells (LCFU) and hematopoietic stem cells (NCFU) was examined. A dose of 10 mg/mouse of dThd given within 1 h before FUra enhanced FUra cytotoxicity to NCFU by a factor of about 4. This effect was also reflected in the reduction of the LD10. The dose-survival curve of FUra in AKR leukemia was modified by the prior administration of dThd 10 mg/mouse: the cytotoxic effect of FUra was enhanced by a factor of between 100 and 1000 throughout the dose range studied. These findings were reflected in the ILS studies. When given by 'high dose' infusion dThd had only a slight antitumor effect on AKR leukemia, and no effect on L1210. When large doses of dThd were infused concomitantly with FUra they potentiated its cytotoxicity against NCFU, AKR LCFU, and L1210 LCFU in a dose-dependent manner and by a maximum factor of about 70.
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PMID:Schedule-dependent antitumor and toxic effects of thymidine and 5-fluorouracil in AKR and L1210 leukemias. 379 55


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