Corpus ID: 176748

N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea, a novel agent equally cytotoxic to nonproliferating human colon adenocarcinoma cells.

  title={N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea, a novel agent equally cytotoxic to nonproliferating human colon adenocarcinoma cells.},
  author={Peter J. Houghton and Frank C. Bailey and Glen S. Germain and Gerald Burr Grindey and Brigitte Witt and Janet A. Houghton},
  journal={Cancer research},
  volume={50 2},
Diarylsulfonylureas have been shown to have therapeutic activity against rodent and human tumor models, notably causing regressions in some lines of human colon adenocarcinomas in mice. At present the mechanism of cytotoxicity is unknown, although preliminary data implicate mitochondria as a potential site of action. In this study, the cytotoxicity of the diarylsulfonylurea N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea (ISCU) has been examined in GC3/c1 human colon adenocarcinoma cells. At… Expand
Characterization of the intracellular distribution and binding in human adenocarcinoma cells of N-(4-azidophenylsulfonyl)-N'-(4-chlorophenyl)urea (LY219703), a photoaffinity analogue of the antitumor diarylsulfonylurea sulofenur.
The results demonstrated that against the human colon adenocarcinoma cell line GC3/c1, LY 219703 is a more potent cytotoxic agent than N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)urea (Sulofenur; ISCU), whereas a subline selected for resistance to ISCU was cross-resistant to LY219703, suggesting a similar mechanism of action or resistance. Expand
Mechanism of killing of HeLa cells by the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY 181984)
The morphological observations suggest that the drug may somehow interfere with the ability of the cells to enlarge following cytokinesis, and the antitumor sulfonylureas appear to inhibit both mitochondrial activity in susceptible human colon lines and to inhibit the oxidation of NADH by isolated plasma membrane vesicles from HeLa cells. Expand
Effect of antitumor diarylsulfonylureas on in vivo and in vitro mitochondrial structure and functions.
The mechanism of action of diarylsulfonylureas, by uncoupling mitochondrial oxidative phosphorylation, may lower cellular ATP and is probable that this mechanism contributes, at least partially, to cytotoxicity in GC3/c1 cells exposed to high concentrations of ISCU for relatively brief periods and possibly contributes to cytOToxicity at drug concentrations that can be achieved in rodents. Expand
Synthesis and cytotoxic evaluation of substituted sulfonyl-N-hydroxyguanidine derivatives as potential antitumor agents.
A series of sulfonyl-N-hydroxyguanidine derivatives was designed and synthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984 and exhibited the greatest growth inhibition of solid tumor cell lines. Expand
Antitumor activity of 4-phenyl-1-arylsulfonylimidazolidinone, DW2143.
Results indicate that the novel sulfonylurea derivative, DW2143, is an attractive candidate for further development as a useful oral anticancer drug. Expand
Proliferation-dependent and -independent cytotoxicity by antitumor diarylsulfonylureas. Indication of multiple mechanisms of drug action.
Analysis of DNA by agarose gel electrophoresis showed that in GC3/c1 cells nucleosomal ladders were formed only when proliferating cells were exposed to ISCU, indicating several mechanisms by which diarylsulfonylurea antitumor agents may cause cell death. Expand
2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers.
Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. Expand
Inhibition of the NADH oxidase activity of plasma membranes isolated from xenografts and cell lines by the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY 181984) correlates with drug susceptibility of growth
The findings suggest a possible correlation between inhibition of plasma membrane NADH oxidase activity by the antitumor sulfonylurea-susceptible or -resistant tissues or cell lines and their oncolytic action. Expand
Synthesis, DNA-binding ability and evaluation of antitumour activity of triazolo[1,2,4]benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.
A series of triazolobenzothiadiazine-pyrrolobenzodiazepines linked through different alkane spacers have been prepared and one of the compounds 5c elevates the DNA helix melting temperature of the CT-DNA by 2.6 degrees C after incubation for 36 h. Expand
Synthesis and evaluation of cytotoxicity of novel arylsulfonylimidazolidinones containing sulfonylurea pharmacophore
Design and synthesis of novel 4-phenyl-1-arylsulfonylimidazolones3 and 4-phenyl-3-arylsulfonylimidazolones4 and evaluation of their cytotoxic activity against eleven human cancer cell lines and twoExpand


Growth state-specific responsiveness of primary cultures of a nude mouse-xenografted human colon carcinoma to 4'-deoxydoxorubicin and a crude human leukocyte alpha-interferon preparation.
Improved procedures for the seeding of primary cultures from human colon tumors are described, and interferon antagonizes the cytotoxic effect of 4'-deoxydoxorubicin on a growing colon tumor cell population when applied immediately after 4'- deoxydOXorUBicin treatment. Expand
Cell-cycle, phase-specific cell killing by carmustine in sensitive and resistant cells.
It is concluded that alkyltransferase activity may overwhelm other determinants that cause cell-cycle phase specificity to BCNU. Expand
Preparing nuclei from cells in monolayer cultures suitable for counting and for following synchronized cells through the cell cycle.
The method was developed for a cell line of epithelial origin (MCF-7), which is often difficult to trypsinize to single cells, and is suitable for following cultures of synchronized cells through the cell cycle, and for performing differential counts of cells with substantial differences in DNA content. Expand
Mitochondrial membrane potential in living cells.
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  • Biology, Medicine
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Metabolite transport in mitochondria.