Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of amidoethylamino-anthraquinone derivatives bearing either one or two salen (bis(salicylidene)ethylenediamine) moieties complexed with CuII or NiII have been synthesized, and their DNA-binding and cleaving properties examined. The effects of the mono- and di-substituted anthracenedione-salen conjugates on DNA cleavage mediated by topoisomerases I and II have also been determined, as well as their cytotoxicity toward human KB cells. The anthraquinone-salen. NiII conjugates bind to GC-rich sequences in DNA, but do not cleave the macromolecule. By contrast, the anthraquinone-salen. CuII hybrids do not recognize particular nucleotide sequences but efficiently induce single-strand breaks in DNA after activation. The 5,8-dihydroxy-anthraquinone conjugates are more cytotoxic and more potent toward topoisomerase II than the non-hydroxylated analogues, but they are less cytotoxic than the salen-free anthraquinones. The attachment of a salen. CuII complex to the anthraquinone chromophore can confer DNA cleaving properties in vitro, but this is at the expense of cytotoxic activity. Anthraquinone-salen. CuII complexes may find useful employ as footprinting probes for investigating ligand-DNA interactions.
 ...
PMID:Salen-anthraquinone conjugates. Synthesis, DNA-binding and cleaving properties, effects on topoisomerases and cytotoxicity. 887 39

Naturally occurring 1,8-dihydroxyanthraquinones are under consideration as possible carcinogens. Here we wanted to elucidate a possible mechanism of their genotoxicity. All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine. In a cell-free decatenation assay, emodin exerted a stronger, danthron a similar and aloe-emodin a weaker inhibition of topoisomerase II activity than m-amsacrine. Analysis of the chromosomal extent of DNA damage induced by these anthraquinones was performed in mouse lymphoma L5178Y cells. Anthraquinone-induced mutant cell clones showed similar chromosomal lesions when compared to the topoisomerase II inhibitors etoposide and m-amsacrine, but were different from mutants induced by the DNA alkylator ethyl methanesulfonate. These data support the idea that inhibition of the catalytic activity of topoisomerase II contributes to anthraquinone-induced genotoxicity and mutagenicity.
 ...
PMID:Characterization of the genotoxicity of anthraquinones in mammalian cells. 1043 60