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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1999-3-16
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pubmed:abstractText |
The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0. 07 to >10 microM. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 microM. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3, 4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 microM. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Caffeic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorogenic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/HIV Integrase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Succinates,
http://linkedlifedata.com/resource/pubmed/chemical/Tartrates,
http://linkedlifedata.com/resource/pubmed/chemical/chicoric acid
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
497-509
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9986720-Anti-HIV Agents,
pubmed-meshheading:9986720-Base Sequence,
pubmed-meshheading:9986720-Caffeic Acids,
pubmed-meshheading:9986720-Cell Line,
pubmed-meshheading:9986720-Cell Survival,
pubmed-meshheading:9986720-Chlorogenic Acid,
pubmed-meshheading:9986720-Cloning, Molecular,
pubmed-meshheading:9986720-DNA Primers,
pubmed-meshheading:9986720-Drug Resistance, Microbial,
pubmed-meshheading:9986720-HIV Integrase Inhibitors,
pubmed-meshheading:9986720-HIV-1,
pubmed-meshheading:9986720-Humans,
pubmed-meshheading:9986720-Magnetic Resonance Spectroscopy,
pubmed-meshheading:9986720-Structure-Activity Relationship,
pubmed-meshheading:9986720-Succinates,
pubmed-meshheading:9986720-Tartrates,
pubmed-meshheading:9986720-Virus Replication
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pubmed:year |
1999
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pubmed:articleTitle |
Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication.
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pubmed:affiliation |
Department of Microbiology and Molecular Genetics, University of California, Irvine, California 92697-4800, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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