DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.

  title={DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.},
  author={Yves Pommier and Elisabetta Leo and Hongliang Zhang and Christophe H. Marchand},
  journal={Chemistry \& biology},
  volume={17 5},
Phenanthriplatin Acts as a Covalent Topoisomerase II Poison
The monofunctional platinum anticancer agent phenanthriplatin, cis-[Pt(NH 3 ) 2 (phenanthridine)Cl](NO 3 ), is shown here to act as a Top2 poison in addition to its known modes of action as a DNA and RNA polymerase inhibitor.
Topoisomerase II Inhibitors: Chemical Biology
Some of the approved agents that target topoisomerase II, as well as some of the newer compounds that may have clinical promise, are surveyed.
Structural Basis of Type II Topoisomerase Inhibition by the Anticancer Drug Etoposide
The crystal structure of a large fragment of human TOP2β complexed to DNA and to the anticancer drug etoposide is presented to reveal structural details of drug-induced stabilization of a cleavage complex and the analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy.
Discovery of Novel Topoisomerase II Inhibitors by Medicinal Chemistry Approaches.
In this review, medicinal chemistry approaches are mainly discussed toward the development of potent topo II inhibitors with low toxicities.
DNA topoisomerases as molecular targets for anticancer drugs
This article is a comprehensive review of knowledge about topoisomerases and their inhibitors collected over the years and contains details on the structure–activity relationship of described classes of compounds.
Topoisomerases inhibition and DNA binding mode of daunomycin–oligoarginine conjugate
The biochemical characterisation of a daunomycin oligopeptide conjugate containing six residues of arginine is reported, by the analysis of its fluorescence properties, DNA interaction and topoisomerases inhibitory effects.
The antitumor activity of CYB-L10, a human topoisomerase IB catalytic inhibitor
This work systematically study the antitumor activity of CYB-L10, a novel indolizinoquinolinedione TOP1 catalytic inhibitor discovered in the laboratory that mainly acts on TOP1 in cancer cells and is not a substrate of the P-glycoprotein.


Topoisomerase I inhibitors: camptothecins and beyond
  • Y. Pommier
  • Chemistry, Biology
    Nature Reviews Cancer
  • 2006
The mechanisms and molecular determinants of tumour response to TOP1 inhibitor are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage.
Recent advances in bacterial topoisomerase inhibitors.
The mechanism of topoisomerase I poisoning by a camptothecin analog
The x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan suggests that there are at least two classes of mutations that can produce a drug-resistant enzyme.
Topoisomerase I inhibitors: selectivity and cellular resistance.
Topoisomerase I (top1) inhibitors (camptothecins and other structurally diverse compounds) are effective and promising anticancer agents. Determinants of selectivity toward cancer cells and
DNA topoisomerases as targets for the anticancer drug TAS-103: primary cellular target and DNA cleavage enhancement.
DNA complex shows that TAS-103 binds to human topoisomerase IIalpha in the absence of DNA, suggesting that enzyme-drug interactions play a role in formation of the ternary topoisomersase II.
Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies
It is shown here that VP-16-induced carcinogenesis involves mainly the β rather than the α isozyme of Top2, suggesting the importance of developing Top2α-specific anticancer drugs for effective chemotherapy without the development of treatment-related secondary malignancies.
Topoisomerase II as a target for anticancer drugs: when enzymes stop being nice.
Repair of topoisomerase I-mediated DNA damage.
The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives
The use of γ-H2AX as a pharmacodynamic biomarker for the clinical development of the indenoisoquinolines is discussed, which results in the rapid and sustained phosphorylation of histone H2AX.