Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-11-23
pubmed:abstractText
Anilinoacridines have recently been found to possess antiparasitic activity toward Leishmania, Trypanosoma, and Plasmodium species. These compounds have been examined for their ability to generate cleavable complex, the protein-associated DNA lesion characteristic of topoisomerase II involvement, in intact L. chagasi promastigotes. At cytotoxic concentrations, anilinoacridine compounds give cleavable complex in a whole cell assay which suggests that the drugs affect a nuclear topoisomerase II in the parasite. Linearization of kinetoplast DNA minicircles also occurs in parasites treated with anilinoacridines at similar concentrations. Exonuclease digestions reveal that the linearized minicircles are blocked at the 5' end but not at the 3' end, further implicating a kinetoplast topoisomerase II in the cleavage process. Interestingly, cytotoxic alkylaminoacridines did not stimulate the production of cleaved DNA in the same experiments. DNA binding experiments showed no apparent correlation between the affinity of the compounds for DNA and antileishmanial activity. Although multiple cytotoxic mechanisms are likely at work, these experiments suggest that topoisomerase II enzyme(s) are affected by antileishmanial anilinoacridines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Cleavable complex formation in Leishmania chagasi treated with anilinoacridines.
pubmed:affiliation
Department of Chemistry, University of Virginia, Charlottesville 22901.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't