Linked Life Data

14567546

Source:http://linkedlifedata.com/resource/pubmed/id/14567546

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-10-21
pubmed:abstractText
Various 1-arylidene-2-tetralones 1 had been shown previously to possess moderate cytotoxic properties unaccompanied by murine toxicity. The objective of the present investigation was to undertake different molecular modifications of representative members of series 1 with a view to discerning those structural features leading to increased potencies. All compounds were evaluated using human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. The Mannich bases 2, 4, 5 and 7 possessed increased potencies compared to the corresponding unsaturated ketones 1 and in general were potent cytotoxics having IC50 values in the 0.2-10 microM range. QSAR using the cytotoxicity data for 2a-e suggested that potency was positively correlated with the size of the substituents in the arylidene aryl ring. Compounds 2a-f were evaluated using a panel of approximately 53 human tumour cell lines and, when all cell lines were considered, were more potent than the reference drug melphalan. In particular, marked antileukemic activity was displayed. Molecular modeling was utilized in order to evaluate whether the shapes of the different compounds contributed to the varying potencies observed. Representative compounds demonstrated minimal or no inhibiting properties towards human N-myristoyltransferase (NMT) and did not bind to calf thymus DNA. This study has revealed a number of unique lead molecules as candidate anti-neoplastic agents serving as prototypes for future development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1475-6366
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-24
pubmed:dateRevised
2007-3-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Cytotoxic mannich bases of 1-arylidene-2-tetralones.
pubmed:affiliation
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. dimmock@skyway.usask.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't