Nuclear targeting and retention of anthracycline antitumor drugs in sensitive and resistant tumor cells.

@article{Taatjes2001NuclearTA,
  title={Nuclear targeting and retention of anthracycline antitumor drugs in sensitive and resistant tumor cells.},
  author={Dylan J. Taatjes and Tad H. Koch},
  journal={Current medicinal chemistry},
  year={2001},
  volume={8 1},
  pages={
          15-29
        }
}
Recent and new results which support a drug-DNA covalent bonding mechanism for cell toxicity of the clinical antitumor drugs, daunorubicin, doxorubicin, and epidoxorubicin, are summarized. The mechanism involves the iron complex of the drugs inducing oxidative stress to yield formaldehyde, which then mediates covalent attachment to G-bases of DNA. At NGC sites the combination of covalent and non-covalent drug interactions serve to virtually crosslink the DNA. Structural data for virtual… 
Anthracycline-formaldehyde conjugates and their targeted prodrugs.
TLDR
The sequence of research leading to a proposal for anthracycline cross-linking of DNA is presented and a promisinglead design is pentyl PABC-Doxaz, targeted to aÂcarboxylesterase enzyme overexpressed in liver cancercells and/or colon cancer cells.
Activation of clinically used anthracyclines by the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate
TLDR
Although apoptosis assays indicated a greater than additive effect for epirubicin/AN-9 combinations, this effect was much more pronounced for doxorubic in/AN -9 combinations.
Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase II
TLDR
As a first-in-class anticancer quinolone derivative, voreloxin is a toposiomerase II-targeting agent with a unique mechanistic signature and may advance the understanding of structure-activity relationships to develop safer and more effective topoisomerase I-targeted therapies for the treatment of cancer.
[Molecular mechanisms of anthracyclines action].
TLDR
Recent progress in understanding the molecular mechanisms of anthracycline action and the new approaches which are being undertaken to improve their therapeutic index are reviewed.
The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines
TLDR
The aim of this study was to examine the role of reductive activation of DOX by the human liver NADPH cytochrome P450 reductase (CPR) in increasing its cytotoxic activity especially in regard to MDR tumour cells.
Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity
TLDR
An overview of issues confirms that anthracyclines remain “evergreen” drugs with broad clinical indications but have still an improvable therapeutic index.
Anthracyclines and mitochondria.
TLDR
The potential role of mitochondria in the molecular mechanisms underlying anthracycline anticancer activity as well as in the pathogenesis of anthrACYcline-induced cardiotoxicity is reviewed.
Synergistic Effect of Endogenous and Exogenous Aldehydes on Doxorubicin Toxicity in Yeast
TLDR
Using several S. cerevisiae strains, their sensitivity to aldehydes and to their combination with doxorubicin, cisplatin, and etoposide was determined and the potential use of aldeHydes and cytotoxic drugs could potentially lead to applications intended to enhance anthracycline-based therapy.
...
...