Linked Life Data

1495008

Source:http://linkedlifedata.com/resource/pubmed/id/1495008

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1992-9-4
pubmed:abstractText
The antiviral/antitumor marine alkaloid dercitin was used as a lead compound to design analogues with anti-HIV and tumor inhibitory activities. Deletion of structural features contributing to cytotoxicity led to analogues with lowered T-lymphocyte toxicity profiles. One compound, 5, induced complete protection against HIV-1 infectivity in vitro at 12.5 micrograms/mL (38 microM) without T-cell toxicity up to 400 micrograms/mL. Compound 4 and 5 also inhibited the binding of HIV-1 to H-9 lymphocytes. These compounds may exert antiviral activity by a unique dual extracellular and intracellular mode of action--both preventing viral attachment to lymphocytes as well as intercalating with viral nucleic acid. Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5 microM concentration compared to a 70 microM dose level of 5-fluorouracil. A means of molecular separation of antiviral activity from cytotoxicity was thus achieved, and putative pharmacophores for antiviral and antitumor actions of the prototype molecule dercitin have been deduced. The 2-thio-9-acridinone derivatives 4 and 5 represent a new structural type exhibiting activity against HIV in vitro, serving as chemical leads in the design of anti-AIDS agents, while thiazolo[5,4-b]acridines such as 2 provide leads in the drug design of new antitumor agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2744-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
HIV-1 neutralization and tumor cell proliferation inhibition in vitro by simplified analogues of pyrido[4,3,2-mn]thiazolo[5,4-b]acridine marine alkaloids.
pubmed:affiliation
Department of Organic Chemistry, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228-0147.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.