Correlation between the formation of cleavable complex with topoisomerase I and growth-inhibitory activity for saintopin-type antibiotics.

@article{Fujii1997CorrelationBT,
  title={Correlation between the formation of cleavable complex with topoisomerase I and growth-inhibitory activity for saintopin-type antibiotics.},
  author={N. Fujii and Y. Yamashita and T. Mizukami and H. Nakano},
  journal={Molecular pharmacology},
  year={1997},
  volume={51 2},
  pages={
          269-76
        }
}
New saintopin-type antibiotics (e.g., saintopin, saintopin E, UCE1022, UCE6) with a naphthacene-dione structure have been discovered through our mechanistically oriented screening using purified mammalian DNA topoisomerases. Saintopin is a dual inducer of topoisomerase I- and topoisomerase II-mediated DNA cleavages in a cell-free system using purified enzymes, whereas others induced topoisomerase I- but not topoisomerase II-mediated DNA cleavage. The order of topoisomerase I-mediated DNA… Expand
Recognition of specific sequences in DNA by a topoisomerase I inhibitor derived from the antitumor drug rebeccamycin.
TLDR
The unique DNA binding characteristics of the rebeccamycin analogue correlate well with its inhibitory effects on topoisomerase I, and seems to be highly sensitive to any modification of the exocyclic substituents on the bases in both the major and minor grooves of the double helix. Expand
Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme.
TLDR
The present review describes the topoisomerase I catalytic mechanisms with particular emphasis on the cleavage complex that represents the enzyme's catalytic intermediate and the site of action for camptothecins. Expand
Design and development of novel DNA Topoisomerase inhibitors.
TLDR
Preliminary data suggests that it may be feasible to selectively deliver potent cytotoxic agents to the site of a tumour by exploiting the proteolytic capacity of over-expressed MMPs in the tumour environment. Expand
Dual topoisomerase I/II inhibitors
TLDR
In this review, the most important and promising dual topo I/II inhibitors designed as anticancer agents will be discussed. Expand
Dual topoisomerase I/II poisons as anticancer drugs.
  • W. Denny
  • Biology, Medicine
  • Expert opinion on investigational drugs
  • 1997
TLDR
No overall structure-activity relationships are discernible for this property, but small structural changes within a particular series appear to markedly alter the relative activities of analogues towards the two enzymes, which supports the 'drug stacking' model of interaction. Expand
UCT1072s, new antitumor antibiotics with topoisomerase II mediated DNA cleavage activity, from Aspergillus sp.
TLDR
This work has screened microbial metabolites and plant extracts for their ability to induce topoisomerase II mediated DNA cleavage in vitro and identified a specific new topoisomease II poison that results in increased DNAstrand breaks. Expand
Diversity of DNA topoisomerases I and inhibitors.
TLDR
The molecular interactions of camptothecin with the top1 cleavage complexes are discussed as well as the mechanisms of selective killing of cancer cells. Expand
Interaction between natural compounds and human topoisomerase I
TLDR
This review points out the interaction between human Top1 and some natural compounds, such us terpenoids, flavonoids, stilbenes and fatty acids, and different assays that can be used to identify the catalytic step of the enzyme inhibited by different natural compounds. Expand
UCE6, a new antitumor antibiotic with topoisomerase I-mediated DNA cleavage activity produced by actinomycetes: producing organism, fermentation, isolation and biological activity.
TLDR
UCE6 exhibited growth inhibitory activity against HeLa S3, HCT116 and Lu-65 cells comparable to that of camptothecin and addition of silicone oil antifoam agent, KS69, to the fermentation enhanced the production of UCE6 by approximately 3 fold. Expand
Novel selective inhibitors for human topoisomerase I, BM2419-1 and -2 derived from saintopin.
TLDR
It was shown that these novel compounds were artifacts derived from saintopin, a dual inhibitor of topoisomerase I and II by independent processes to inhibited selectively the yeast growth dependent on human topoisomersase I induction. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 39 REFERENCES
Induction of mammalian DNA topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus.
TLDR
Saintopin represents a new class of antitumor agent that can induce both mammalian DNA topoisomerase I and mammalianDNA topisomerase II mediated DNA cleavage. Expand
Saintopin, a dual inhibitor of DNA topoisomerases I and II, as a probe for drug-enzyme interactions.
TLDR
The "drug-stacking" model proposes that topoisomerase inhibitors bind, possibly through hydrogen bonding and/or stacking, with one of the bases flanking the DNA termini and within the enzyme catalytic pocket, most likely by stacking with the catalytic tyrosine. Expand
Saintopin, a new antitumor antibiotic with topoisomerase II dependent DNA cleavage activity, from Paecilomyces.
TLDR
In order to identify a specific new topoisomerase II poison, screened cultures of actinomycetes and fungi for their ability to induce TDC in vitro and isolated a novel compound with TDC activity, saintopin, from the culture broth of Paecilomyces sp. Expand
Induction of topoisomerase II-mediated DNA cleavage by the plant naphthoquinones plumbagin and shikonin.
TLDR
Plumbagin and shikonin induced a similar DNA cleavage pattern with topoisomerase II which was different from the cleavage patterns induced with other known topoisomersase II-active drugs. Expand
Induction of mammalian DNA topoisomerase I mediated DNA cleavage by antitumor indolocarbazole derivatives.
TLDR
The results indicate that KT6006 and KT6528 represent a new distinct class of mammalian DNA topoisomerase I active antitumor drugs that have different properties with respect to their interaction with DNA. Expand
Induction of a heat-stable topoisomerase II-DNA cleavable complex by nonintercalative terpenoides, terpentecin and clerocidin.
TLDR
It is shown that terpentecin and clerocidin induce topoisomerase II-mediated DNA cleavage in vitro with comparable potency to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside, suggesting that topoisomersase II is a cellular target for these drugs. Expand
Sequence selectivity of topoisomerase II DNA cleavage stimulated by mitoxantrone derivatives: relationships to drug DNA binding and cellular effects.
TLDR
The DNA cleavage efficiencies of the tested drugs at low concentrations correlated with the DNA binding affinity, which suggests that all tested drugs share a similar specificity for interaction with sites recognized by the enzyme. Expand
DNA minor groove-binding ligands: a different class of mammalian DNA topoisomerase I inhibitors.
TLDR
The results suggest that MGBLs, like camptothecin, abort Topo I reactions by trapping reversible cleavable complexes, and DNA topoisomerase (Topo) I may be a pharmacological target of M GBLs. Expand
Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin.
TLDR
The results suggest that camptothecin interferes with DNA topoisomerase I both in cultured mammalian cells and in the purified system by trapping a reversible enzyme-DNA cleavable complex. Expand
Unique sequence specificity of topoisomerase II DNA cleavage stimulation and DNA binding mode of streptonigrin.
TLDR
The results indicate that streptonigrin may bind to the DNA in a manner similar to that of minor groove binders and that its pharmacophore, possibly different from other topoisomerase II inhibitors, may be an important determinant of its unique sequence position specificity. Expand
...
1
2
3
4
...