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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
1992-9-4
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pubmed:abstractText |
Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided fractionation of an extract of Calophyllum lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against HIV-1 replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, respectively), but were inactive against HIV-2. Some of the related compounds also showed evidence of anti-HIV-1 activity. Studies with purified bacterial recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 specific RT inhibitors. Moreover, calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-HIV chemotype for drug development.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2735-43
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:1379639-Antiviral Agents,
pubmed-meshheading:1379639-Chromatography, Liquid,
pubmed-meshheading:1379639-Coumarins,
pubmed-meshheading:1379639-Cytopathogenic Effect, Viral,
pubmed-meshheading:1379639-Drug Resistance, Microbial,
pubmed-meshheading:1379639-HIV Reverse Transcriptase,
pubmed-meshheading:1379639-HIV-1,
pubmed-meshheading:1379639-HIV-2,
pubmed-meshheading:1379639-Humans,
pubmed-meshheading:1379639-Hydrolysis,
pubmed-meshheading:1379639-Magnetic Resonance Spectroscopy,
pubmed-meshheading:1379639-Pyranocoumarins,
pubmed-meshheading:1379639-Reverse Transcriptase Inhibitors,
pubmed-meshheading:1379639-Structure-Activity Relationship,
pubmed-meshheading:1379639-Trees,
pubmed-meshheading:1379639-Tumor Cells, Cultured,
pubmed-meshheading:1379639-Virus Replication
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pubmed:year |
1992
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pubmed:articleTitle |
The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum.
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pubmed:affiliation |
Laboratory of Drug Discovery Research and Development, Frederick Cancer Research and Development Center (NCI-FCRDC), Maryland 21702-1201.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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