Linked Life Data

7837221

Source:http://linkedlifedata.com/resource/pubmed/id/7837221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-2-28
pubmed:abstractText
The influence of the 3-substituent on the cytotoxicity of the 6-aziridinylpyrrolo[1,2-a]-benzimidazole quinones (PBIs), the 6-acetamidopyrrolo[1,2-alpha]benzimidazole quinones (APBIs), and the 6-acetamidopyrrolo[1,2-alpha]benzimidazole iminoquinones (imino-APBIs) was investigated by comparing LC50 mean graphs consisting of 60 cancer lines. Increasing lipophilicity of the 3-substituent of PBIs and APBIs increased the cytotoxicity specifically in melanoma cell lines. The 3-substituent does not influence DNA cleavage by reduced PBIs, except for the 3-carbamate derivative which shows enhanced cleavage. This property of the 3-carbamate is rationalized in terms of the PBI major groove binding model. The imino-APBIs show enhanced cytotoxicity in melanoma and renal cancer cell lines; the correlation coefficient for log LC50 vs log lipophilicity is 0.8 to 0.9. COMPARE correlations revealed that the PBIs are activated by DT-diaphorase but that the APBIs and imino-APBIs are inactivated by this enzyme. Thus, the latter two agents are cytotoxic only as quinones. It was noted that APBIs possess a similar cytotoxic profile to three anthracycline analogues. This observation suggests mechanistic similarities between both types of cytotoxic agents. Major conclusions of this study pertain to the design of agents displaying cytotoxicity specifically against melanoma and renal cancers and to the use of 60-cell line mean graphs and COMPARE in cancer drug QSAR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Pyrrolo[1,2-a]benzimidazole-based quinones and iminoquinones. The role of the 3-substituent on cytotoxicity.
pubmed:affiliation
Department of Chemistry and Biochemistry, Arizona State University, Tempe 85287-1604.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't