PubMed Health⌕ Search

Biomedical subjects

I Bursuker

Publications and source records attributed to I Bursuker.

At least 19 recordsLinked to original sources
PubMed2001

Isolation, synthesis, and structure-activity relationships of bioactive benzoquinones from Miconia lepidota from the Suriname rainforest.

Bioactivity-directed fractionation of an EtOAc extract from the leaves of Miconia lepidota afforded the two benzoquinones 2-methoxy-6-heptyl-1,4-benzoquinone (1) and 2-methoxy-6-pentyl-1,4-benzoquinone (primin) (2). This is the first reported isolation of 1. Both quinones 1 and 2 exhibited activity toward mutant yeast strains based on Saccharomyces cerevisiae, indicative of their cytotoxicity and potential anticancer activity. A number of previously synthesized and new analogues were prepared and tested in the same strains. Compounds 1, 2, 2-methoxy-6-butyl-1,4-benzoquinone (5), and 2-methoxy-6-decyl-1,4-benzoquinone (6) were tested in two cytotoxicity assays. In the M109 tumor cell lines, quinones 1, 2, and 6 had an IC(50) value of 10 microg/mL. In the A2780 cell line, compounds 1, 2 and 5 had IC(50) values of 7.9, 2.9, and 3.2 microg/mL, respectively.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Bioactive saponins from Swartzia schomburgkii from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Swartzia schomburgkii using the engineered yeast strains 1138, 1140, and 1353 as the bioassay tool resulted in the isolation of five active (2, 4-7) and three inactive (1, 3, 8) saponins. Saponins 4 and 6 are previously unreported. The structures of all of the saponins were established based on 1D and 2D NMR spectral analysis, on acid and alkaline hydrolysis followed by TLC and GC-MS, and by comparison with literature data for known compounds. Three of the isolated compounds (4-6) showed weak cytotoxicity against the M-109 cell line.

Antifungal Agents↗
PubMed1999

Synthesis and biological evaluation of analogues of cryptolepine, an alkaloid isolated from the Suriname rainforest.

Bioassay-guided fractionation of an extract of a mixture of Microphilis guyanensis and Genipa americanacollected in the rainforest of Suriname yielded the known alkaloid cryptolepine (2) as the major active compound in a yeast bioassay for potential DNA-damaging agents; the same compound was later reisolated from M. guyanensis. The structure of cryptolepine was identified unambiguously by spectral data and by its total synthesis. Several cryptolepine derivatives (3-29, 32-41) were synthesized based on modifications of the C-2, N-5, N-10, and C-11 positions. Two cryptolepine dimers (30, 31) were also prepared. The structure modifications did not result in compounds with a higher potency than the parent compound cryptolepine in the yeast assay system, although some derivatives did show significant activity. Selected compounds (6, 7, 17, 22, 23, 26, and 27) were also tested for cytotoxicity in mammalian cell culture, and two compounds showed significant cytotoxic activity.

Alkaloids↗
PubMed1998

DNA-damaging steroidal alkaloids from Eclipta alba from the suriname rainforest1.

Bioassay-guided fractionation of the MeOH extract of Eclipta alba using three yeast strains (1138, 1140, and 1353) resulted in the isolation of eight bioactive steroidal alkaloids (1-8), six of which are reported for the first time from nature. The major alkaloid was identified as (20S)(25S)-22,26-imino-cholesta-5,22(N)-dien-3beta-ol (verazine, 3), while the new alkaloids were identified as 20-epi-3-dehydroxy-3-oxo-5,6-dihydro-4,5-dehydroverazine (1), ecliptalbine [(20R)-20-pyridyl-cholesta-5-ene-3beta,23-diol] (4), (20R)-4beta-hydroxyverazine (5), 4beta-hydroxyverazine (6), (20R)-25beta-hydroxyverazine (7), and 25beta-hydroxyverazine (8). Ecliptalbine (4), in which the 22,26-imino ring of verazine was replaced by a 3-hydroxypyridine moiety, had comparable bioactivity to verazine in these assays, while a second alkaloid (8) showed good activity against Candida albicans. All the alkaloids showed weak cytotoxicity against the M-109 cell line.

Alkaloids↗
PubMed1997

Interaction of NT-4 and BDNF with gp145trkb receptor: effect on cellular metabolism.

In the present study a silicon microphysiometer (Cytosensor) was applied in investigating interactions of gp145(trkb), a member of the tyrosine kinase receptor family, with different neurotrophic factors. NIH-3T3 cells transfected with gp145(trkb) receptors (NIH3T3/trkB cells) were utilized in the studies. Treatment with brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and neurotrophin-3 (NT-3) induced changes in the metabolic rate of NIH3T3/trkB cells. In contrast, no response was observed with nerve growth factor (NGF). The effects of NT-4 and BDNF on NIH3T3/trkB cells were receptor-specific in that they did not induce metabolic rate changes in wild type NIH3T3 cells or cells transfected with either gp140(trkb) (TrkA) or gp145(trkb) (TrkC) receptors. In contrast, NT-3 induced metabolic rate changes in cells transfected with each of the three different Trk receptors. The activity of NT-4 was significantly higher than that of BDNF. K252a, a protein kinase inhibitor, reduced the NT-4- and BDNF-induced response of the NIH3T3/trkB cells. This suggests that the NT-4 and BDNF-induced metabolic rate changes are associated with autophosphorylation of the tyrosine protein kinase residues. This hypothesis is further supported by results of western blot analysis. The results show that interactions of Trk receptors with neurotrophic factors result in metabolic changes in cells expressing the receptors.

3T3 Cells↗
PubMed1995

Rakicidins, new cytotoxic lipopeptides from Micromonospora sp. fermentation, isolation and characterization.

The new cytotoxic agents rakicidins A and B were isolated from cultured broth of a Micromonospora sp. Spectroscopic and amino acid analysis has shown that rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2,4-dienoic acid, 3-hydroxy-2,4,16-trimethyl-heptadecanoic acid, sarcosine, and 3-hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side chain. These compounds exhibited cytotoxicity against the M109 cell line.

Animals↗
PubMed1993

Identification of functional domains in murine granulocyte-macrophage colony-stimulating factor using monoclonal antibodies to synthetic peptides.

Granulocyte-macrophage (GM)-CSF is an important hematopoietic cytokine that regulates proliferation and differentiation of macrophages, neutrophils, and eosinophils. In this study, we generated mAb to five synthetic peptides that correspond to regions along the murine GM-CSF molecule. The ability of anti-peptide mAb to bind to and inhibit biologic activity of murine (m) GM-CSF was determined. mAb with the highest neutralization titers were derived from mice immunized with peptide II, which correspond to amino acids 27 to 38 of mGM-CSF. Immunochemical studies showed that peptide II specifically blocked binding of anti-peptide II mAb to GM-CSF. mAb to two other peptides in the N-terminal half corresponding to residues 7 to 17 and 47 to 58, respectively, of mGM-CSF also inhibited GM-CSF-dependent proliferation and differentiation of murine bone marrow precursors for macrophages and granulocytes. Anti-peptide mAb also inhibited growth of a murine hematopoietic cell line FDCP1 and a murine T cell line HT-2, which was shown to be dependent on GM-CSF for growth in vitro. Biologic activity of both natural and recombinant mGM-CSF was neutralized by anti-peptide mAb. These findings indicate that epitopes in the N-terminal region of mGM-CSF are important for biologic activity, and the epitope defined by peptide II (residues 27 to 38) lies within a particularly important functional domain of the mGM-CSF molecule.

Amino Acid Sequence↗
PubMed1993

Granulocyte-macrophage colony-stimulating factor plays a role in the functional activity of mast cells.

A peptide homologous to a region of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), P27-38, which was shown to be a GM-CSF antagonist, inhibited the function of serotonin release from murine mast cells. Peptide P27-38 inhibited immunoglobulin E (IgE)-mediated serotonin release in a dose-dependent manner when induced by either specific antigen or anti-IgE antibody. In contrast, non-receptor-mediated release of serotonin by agents such as compound 48/80 or the calcium ionophore A23187 were not affected by the GM-CSF antagonist. Similar effects were observed with GM-CSF-neutralizing antibodies. The inhibitory effect of P27-38 and the neutralizing antibodies on serotonin release could be reversed by the addition of exogenous GM-CSF to the stimulated mast cells, indicating that the inhibitory activity was probably due to an effect on endogenously produced GM-CSF. These findings suggest that GM-CSF produced by stimulated mast cells is involved in the regulation of their activity in an autocrine manner.

Amino Acid Sequence↗
PubMed1992

In vivo regulation of hemopoiesis by transforming growth factor beta 1: stimulation of GM-CSF- and M-CSF-dependent murine bone marrow precursors.

Injection of mice with either natural bovine bone-derived or human recombinant transforming growth factor beta 1 (TGF-beta 1) resulted in a significant increase of the macrophage and macrophage-granulocyte-forming capacity of their macrophage colony-stimulating factor (M-CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow precursor cells. The increased potential for generating granulocytes and/or macrophages from bone marrow cells of mice injected with TGF-beta 1 was associated with an increase of the number of M-CSF- and GM-CSF-dependent bone marrow colony-forming units (CFU). The effect was selective, in that in vivo applied TGF-beta 1 did not affect interleukin 3 (IL-3)-dependent CFU. The data suggest that TGF-beta may be useful in recovery of bone marrow granulocyte- and macrophage-forming potentials following depletion caused by chemo- or radiotherapy.

Animals↗
PubMed1991

Immunomodulation in an apparently non-immunogenic murine tumor.

Madison lung carcinoma (M109), a murine tumor of spontaneous origin, appears to be non-immunogenic, according to 2 commonly employed tests for tumor immunogenicity. However, C.parvum-induced immunopotentiation during the growth of M109 tumor results in post-excision anti-tumor immunity to M109 tumor implants. The C.parvum-potentiated post-excision immunity to M109 is tumor-specific and T-cell-dependent. T cells from mice whose progressive M109 tumors have been excised are capable, on passive transfer, of inhibiting adoptive immunotherapy of T-cell-deficient recipients by spleen cells from mice immunized with an admixture of M109 cells and C.parvum. The data are interpreted as evidence supporting the hypothesis that the apparent lack of anti-tumor immunity in this tumor model is not due to the absence of tumor-associated antigens. We suggest that, instead, in this model the balance between the effector and suppressor arms of the immune response favors tumor-induced immunosuppression, resulting in a magnitude of anti-tumor immunity insufficient for detection by commonly employed tests for tumor immunogenicity. Our study shows that shifting the balance in favor of the effector arm by means of immunopotentiation results in a measurable immune response to an apparently non-immunogenic tumor.

Animals↗
PubMed1990

Production of interferon-gamma by in vivo tumor-sensitized T cells: association with active antitumor immunity.

The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma.

Animals↗
PubMed1987

In vitro expression of secondary antitumor immunity by in vitro tumor-sensitized T cells: inhibition by tumor-induced suppressor T cells.

In vitro cultivation of memory immune cells from P815- or P388-immune mice with corresponding irradiated tumor cells induced generation of cytolytic T cells (CTL). The induction of CTL generation, as well as the cytolytic activity itself, was tumor-specific. The in vitro generation of CTL from P815- or P388-immune cells was suppressed by spleen cells from mice bearing corresponding progressive tumors (tumor size 15 mm). The tumor-induced suppressor cells suppressed the in vitro generation of CTL, but did not affect their cytolytic function. The suppression was tumor-specific and was mediated by Ly1+2-L3T4+ T cells. Treatment of suppressor cell donors with cyclophosphamide or sublethal gamma-radiation completely abolished the ability of their spleen cells to inhibit the in vitro CTL generation.

Animals↗
PubMed1986

Immunological consequences of tumor excision: from active immunity to immunological memory.

Excision of the immunogenic Meth-A fibrosarcoma during generation by the host of concomitant antitumor immunity resulted in the appearance in sequence of two qualitatively distinct states of post-excision immunity. Immunity expressed on the day of excision was dependent on Ly-1-2+, cyclophosphamide-sensitive T cells, whereas immunity expressed 2 weeks later was dependent on cyclophosphamide-resistant T cells which can be functionally eliminated by either anti-Ly-1 or anti-Ly-2 monoclonal antibody and complement. The data suggest that antitumor immunity expressed shortly after tumor excision represents active concomitant immunity that is acquired by the host before excision is performed. In contrast, immunity expressed 2 weeks later is based on immunological memory.

Animals↗
PubMed1985

Suppression of generation of concomitant antitumor immunity by passively transferred suppressor T cells from tumor-bearing donors.

Infusion of normal recipient mice with suppressor T cells from donors bearing a progressive Meth A fibrosarcoma results in a diminished capacity of the recipients to generate concomitant and postexcision antitumor immunity. The passive transfer of suppressor cells which prevented the generation of immunity to the Meth A fibrosarcoma did not affect the capacity of the recipients to reject an allogeneic tumor. The data provides direct evidence in support of the hypothesis that suppressor T cells, generated at later stages of growth of Meth A fibrosarcoma, function to down-regulate an already acquired mechanism of concomitant immunity.

Animals↗
PubMed1984

Generation and decay of the immune response to a progressive fibrosarcoma. I. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells.

It was shown that the progressive growth of the immunogenic meth A fibrosarcoma in its semisyngeneic host results in the generation of concomitant immunity to the growth of a tumor implant. The generation of immunity occurred between days 6 and 9 of tumor growth and was associated with the generation of sensitized T cells that were capable, on passive transfer, of causing regression of a 3-d tumor in gamma-irradiated recipients. After day 9 of tumor growth, concomitant immunity and the T cells able to passively transfer it were progressively lost, and this was associated with the generation of splenic suppressor T cells able to suppress the expression of adoptive immunity against an established tumor in T cell-deficient ( TXB ) recipients. The T cells that passively transferred concomitant immunity were shown to be of the Ly-1-2+ phenotype, in contrast to the T cells that transferred suppression, which were shown with the same reagents to be Ly-1+2-. The results are consistent with the hypothesis that the progressive growth of an immunogenic tumor results in the generation of Ly-1-2+-sensitized effector T cells that fail to reach a number sufficient to destroy the tumor because their generation is down-regulated by tumor-induced Ly-1+2- suppressor T cells.

Animals↗