Linked Life Data

11354310

Source:http://linkedlifedata.com/resource/pubmed/id/11354310

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-5-16
pubmed:abstractText
A series of benzimidazo[2,1-a]isoquinolines with carboxamide side chains at the 1-, 6-, 9- and 11-positions were prepared, in order to study the biological effects of varying the position of the side chain in this tetracyclic series. The 6-, 9- and 11-analogues were obtained by modifications to published chemistry. The 1-carboxamide analogue was obtained via a one-pot isocoumarin/isoquinolone conversion of 3-methylisocoumarin-8-carboxylic acid with o-phenylenediamine in buffered aqueous acid, which gave the required 1-acid. The compounds were evaluated in a panel of cell lines in culture. The 6-carboxamides, where the side chain is attached to one of the central rings, were not active, but the 1- and 11-carboxamides, where the side chain is attached to one of the terminal rings off the chromophore short axis, were reasonably cytotoxic (IC50s < 1 microM). Overall, the structure-activity relationships are broadly in line with those seen with other tri- and tetracyclic carboxamides, and are consistent with recent crystal structure studies of acridine-4-carboxamides bound to DNA. The most potent 1-carboxamide was highly active in vivo against s.c. colon 38 tumours in mice, providing a growth delay of 12 days.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0266-9536
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
339-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Synthesis and cytotoxic activity of carboxamide derivatives of benzimidazo[2,1-a]isoquinoline and pyrido[3',2':4,5]imidazo[2,1-a]isoquinoline.
pubmed:affiliation
Chemistry Department, La Trobe University, Bundoora, Victoria, Australia. l.deady@latrobe.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't