Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1994-3-21
pubmed:abstractText
Recently, a number of novel quinolones with potent activity against topoisomerase II and eukaryotic cells have been described. Many of these compounds contain aromatic substituents in their C-7 ring positions. To determine whether pyrimido[1,6-a]benzimidazoles, a class of drugs modeled on quinolones, also display activity toward eukaryotic systems, the effects of Ro 46-7864 and Ro 47-3359 on Drosophila melanogaster topoisomerase II and Kc cells were characterized. While the former drug contains an aliphatic group (4-N-methylpiperazine) at the ring position equivalent to C-7 in quinolones, the latter compound contains an aromatic substituent (2,6-dimethylpyridine). Both pyrimido[1,6-a]benzimidazoles inhibited DNA relaxation catalyzed by the type II enzyme. However, only Ro 47-3359 enhanced topoisomerase II-mediated DNA cleavage and was toxic to Kc cells. At a concentration of 100 microM, this drug approximately doubled the levels of DNA breakage in vitro and killed > 50% of the initial cell population of cultures. These results strongly suggest that selected pyrimido[1,6-a]benzimidazoles may function as topoisomerase II-targeted drugs with cytotoxic potential.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1315393, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1316228, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1317151, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1320012, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1323952, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1337067, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1580602, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1650363, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1657531, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1847075, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1850968, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1851170, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1963290, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-1987461, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-200930, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2159323, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2176849, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-226889, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-227840, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2542330, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2549853, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2550774, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2551366, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2556075, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2556080, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2822084, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-2849603, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-3015015, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-337300, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-6267071, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-6305984, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-6308010, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-6308011, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-6317692, http://linkedlifedata.com/resource/pubmed/commentcorrection/8109923-8388196
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0066-4804
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2599-605
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
A pyrimido[1,6-a]benzimidazole that enhances DNA cleavage mediated by eukaryotic topoisomerase II: a novel class of topoisomerase II-targeted drugs with cytotoxic potential.
pubmed:affiliation
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't