Linked Life Data

427824

Source:http://linkedlifedata.com/resource/pubmed/id/427824

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1979-6-29
pubmed:abstractText
The activity of a number of substituted alkylaminoanthraquinones was compared in transplanted murine tumor systems including P388 and L1210 leukemias, B16 melanoma, and colon carcinoma 26. The structure-activity relationships among this class of compounds are discussed. Several derivatives had very high antitumor activity in several tumor systems. Two of the most active derivatives, namely, 1,4-bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (bisalkylAAD) and 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (dihydroxybisalkylAAD), which had curative activity in the above-mentioned tumors, were compared in considerable detail. DihydroxybisalkylAAD showed distinct advantages over bisalkylAAD in several tumor systems and is tenfold more potent with respect to effective dose range. This last difference is important for two reasons. First, these aminoanthraquinones are strong and persistent blue dyes and the administration of lower doses would minimize a potential cosmetic drawback of these compounds. Second and most important, iv administration of dose levels of bisalkylAAD which are within the therapeutic dose range on intermittent dose schedules produced convulsions and immediate death. IV administration of dihydroxybisalkylAAD also caused acute toxicity, but, because of its increased potency relative to antitumor activity and delayed toxicity, this acute toxicity was apparent only at doses well above the therapeutic dose range. All of the aminoanthraquinones evaluated, regardless of their activity as antitumor agents in vivo, proved to be potent inhibitors of DNA and RNA synthesis in vitro and bound strongly to DNA as evidenced by deltaTm values (deltaTm = upward shift in DNA melting temperature). Thus, the strong antitumor activity of aminoanthraquinones would appear to be due to some mechanism other than, or in addition to, DNA binding and inhibition of nucleic acid synthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0361-5960
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
425-39
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1979
pubmed:articleTitle
Experimental antitumor activity of aminoanthraquinones.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.