Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Effect of two pyrimidine analogs on accumulation of tubulin in NHIK 3025 cells (1990)
    Springer
    Molecular and cellular biochemistry 96 (1990), S. 117-126 
    Details
    ISSN: 1573-4919
    Keywords: pyrimidine sulfone ; -sulfoxide ; sulfhydryls ; tubulin accumulation ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Accumulation of tubulin as compared with the accumulation of total cellular protein in human NHIK 3025 cells treated with the sulfone 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) and the sulfoxide 2-(2thenyl)sulfinyl-5-bromopyrimidine (NY 4138), two mitotic inhibitors, were investigated by two-parametric flow cytometry. Following a 4 h treatment with NY 4137 tubulin accumulation is inhibited while total protein continues to accumulate. After treatment for 4h with NY 4138 the accumulation of total protein is approximately constant, while the accumulation of tubulin is reduced although not to the same degree as that found for NY 4137-treated cells. In addition, the percentage tubulin SH-groups (6.89 ± 0.14) remaining after treatment of purified rat brain tubulin with NY 4137 or NY 4138 was determined. Treatment with 0.0125 mM NY 4137 reduced the number of tubulin SH-groups detectable with dithiobis benzoate or from 6.89 ± 0.14 before treatment to about 4 after treatment. However, practically all SH-groups of tubulin remain detectable following treatment with the same concentration of NY 4138. From the results described in this report we infer that NY 4137 binds to tubulin SH-groups and that inhibition of tubulin accumulation follows as a secondary effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00420903
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Inactivation of human cells cultivated in vitro by the new mitotic inhibitors NY 4137 and NY 4138 (1987)
    Springer
    Investigational new drugs 5 (1987), S. 259-266 
    Details
    ISSN: 1573-0646
    Keywords: pyrimidine sulfone ; pyrimidine sulfoxide ; cell inactivation ; age response ; high-performance ; liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of the two closely related drugs, the sulfone 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137), and the sulfoxide 2-(2-thenyl)sulfinyl-5-bromopyrimidine (NY 4138), a sulfoxide, on the survival of cells of the human line NHIK 3025 was investigated. Cell survival was measured as the ability of single cells to form macroscopic colonies. Two-hour treatment with 0.012 mM NY 4137 resulted in 50% inactivation. The drug concentration of NY 4138 had to be adjusted about 10 times higher than that of NY 4137 for treatment periods of 2 or 24 h to obtain similar surviving fraction after treatment of asynchronous cells. Treatment of synchronized NHIK 3025 cells with NY 4137 showed that survival varied little with cell age. Following treatment with NY 4138, however, cells were particularly sensitive in G2 and in mitosis. As the survival curves for both drugs display a plateau region, where increasing the drug dose has little or no effect on cell inactivation, the presence of resistant subpopulations of cells is considered. High-performance liquid chromatography of drug solutions in cell culture medium showed that both NY 4137 and NY 4138 bound to, or were metabolized by, medium and/or cell components. The concentration of NY 4137 in cell culture medium, however, was reduced at a higher rate than NY 4138. The half-life of NY 4137 was on the order of 5 h, while the half-life of NY 4138 was over 24 h. These observations correlate well with the relative chemical reactivities for these drugs in nucleophilic displacement reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175296
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Multipolar mitotic cells in the human cell line NHIK 3025 following treatment with the mitotic inhibitor NY 4137 (1991)
    Springer
    Investigational new drugs 9 (1991), S. 19-28 
    Details
    ISSN: 1573-0646
    Keywords: pyrimidine sulfone ; SH-groups ; tubulin ; centrifugal elutriation ; multipolar mitotic cells ; flowcytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Treatment of human NHIK 3025 cells during interphase with the mitotic inhibitor 2-(2-thenyl) sulfonyl-5-bromopyrimidine (NY 4137) induced the formation of multipolar mitotic cells. A 4 h pulse treatment with 0.010 mM NY 4137 induced the formation of such cells regardless of whether treatment occurred in G1 or S phase. Approximately 35% of the cells originating from such multipolar mitotic divisions had less-than-normal G1 DNA content. Recordings of the DNA content of these small cells by means of flow cytometry showed that the amount of DNA per cell varied randomly. Subpopulations were separated by centrifugal elutriation on the basis of differences in cellular volume. Simultaneous two-parametric recordings of DNA versus total cellular protein showed that even though cells contained an amount of DNA less than G1 cells, there was a proportionality between DNA content and protein content despite variations in cell size.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194540
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Structure-activity relationship of 1-propargyl-5-halopyrimidin-2-ones (1983)
    Springer
    Investigational new drugs 1 (1983), S. 203-211 
    Details
    ISSN: 1573-0646
    Keywords: metahalone ; metaphase arrest ; colchicine ; drug competition ; tubulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The structure-activity relationship of 1-propargyl-5-halopyrimidin-2-ones with respect to mitotic inhibitory potential and inhibition of colchicine binding to tubulin was investigated. A correlation between accumulation in metaphase of cultured human NHIK 3025 cells and drug competition with colchicine binding to tubulin was found for each compound. Effects on division of NHIK 3025 cells were determined in stained preparations following a 6 h treatment with drugs. The four halogen-substituted compounds displayed metaphase arresting ability while the H-substituted 1-propargylpyrimidin-2-one did not. 1-Propargyl-5-fluoropyrimidin-2-one was active at 1.5 and 0.75 mM while the 5-chloro, 5-bromo and 5-iodo compounds caused metaphase arrest at 0.375 and 0.18 mM. The ability of these drugs to compete with colchicine binding to DEAE-cellulose purified tubulin was also investigated. 1-Propargylpyrimidin-2-one at 5 mM did not inhibit (3H)colchicine binding to tubulin as determined by Sephadex G-50 gel filtration. The halogen-substituted pyrimidones, however, demonstrated competitive inhibition of colchicine binding to tubulin. Five mM 1-propargyl-5-iodopyrimidin-2-one inhibited colchicine binding by 43.2%, the highest value obtained within the metahalone group. The drugs tested had no effect on vincristine binding to tubulin. With respect to the halogen substitution, the increasing order of mitotic inhibitory potential and competition with colchicine binding to tubulin is H ≪ F 〈 Cl ≦ Br ≦ I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00208891
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Effects of the new mitotic inhibitor pyrimidinsulfone NY 4137 on human cells in vitro and on colchicine binding to tubulin (1986)
    Springer
    Investigational new drugs 4 (1986), S. 221-229 
    Details
    ISSN: 1573-0646
    Keywords: pyrimidinsulfone ; metaphase arrest ; cell-cycle inhibition ; colchicine ; tubulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) on cells of the human line NHIK 3025 was investigated. It was shown that NY 4137 induces cell cycle specific inhibition in metaphase. A dose-dependent prolongation of metaphase was found and the fraction of cells able to escape metaphase arrest declined gradually as the concentration of NY 4137 increased. A total block in metaphase was achieved with 0.016 mM and higher concentrations of NY 4137. Interphase was also prolonged in cells treated with 0.016 mM. Inhibition of valine incorporation by NY 4137 was also found to be dose-dependent. Following a 2-h exposure to 0.2 mM NY 4137 valine incorporation was inhibited by 80–85%. Inhibition of colchicine and vincristine binding to purified tubulin was also investigated. Double reciprocal plot and gel filtration chromatography showed that NY 4137 competitively inhibited colchicine binding to DEAE-cellulose purified tubulin. NY 4137 had no effect on vincristine binding to tubulin. The binding of NY 4137 to tubulin at or near the colchicine binding site may be responsible for the metaphase arrest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179587
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    In vivo and in vitro pharmacokinetics of 4,6-benzylidene-D-glucose (BG) in rats (1990)
    Springer
    Investigational new drugs 8 (1990), S. 149-157 
    Details
    ISSN: 1573-0646
    Keywords: benzylidene-glucosem ; BG ; HPLC ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In vivo pharmacokinetics of 4,6-benzylidene-D-glucose (BG) was investigated in rats following an i.v. bolus injection of 85 mg BG/kg body weight. High performance liquid chromatography (HPLC) was used to characterize and quantitate BG in whole blood or serum samples. It was found that BG rapidly disappeared with a half-life (t1/2)on the order of 10 min. At the same time a metabolite appeared which eluted before the double isomer peaks of BG. It increased in concentration from 0 to 30 min after initial i.v. injection of BG. Thereafter the metabolite was slowly removed or cleared from the animals. The t1/2 of the metabolite calculated from the time of maximum concentration was found to be about 1 h. BG was also metabolized by whole rat blood at 37°C, but on a different time scale in vitro. The t1/2 of BG in the in vitro assays was now about 4 h, as compared to 10 min in vivo. BG was not metabolized in rat plasma or rat serum. In contrast to in vivo data, the metabolite of BG was not reduced upon further incubation, but remained in blood samples with no reduction for at least 24 h. In addition, we found that protein synthesis was inhibited by approximately 50% when isolated rat hepatocytes were incubated with 3.2 mM BG. BG was slowly metabolized by hepatocytes to produce a metabolite indistinguishable (by HPLC) from that found in blood samples. Analysis of the metabolite by combined gas chromatography-mass spectrometric (GC-MS) methods identified it as being 1,3-benzylidene-D-glucitol. An intracellular reduction of BG by aldose reductase is proposed to occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177250
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...