Abstract
Seventeen lichen acids comprising despides, depsidones, and their synthetic derivatives have been examined for their inhibitory activity against HIV-1 integrase, and two pharmacophores associated with inhibition of this enzyme have been identified. A search of the NCI 3D database of approximately 200,000 structures yielded some 800 compounds which contain one or the other pharmacophore. Forty-two of these compounds were assayed for HIV-1 integrase inhibition, and of these, 27 had inhibitory IC50 values of less than 100 microM; 15 were below 50 microM. Several of these compounds were also examined for their activity against HIV-2 integrase and mammalian topoisomerase I.
MeSH terms
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Binding Sites
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / virology
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Cell Line
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Computer Simulation
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Crystallography, X-Ray
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DNA Topoisomerases, Type I / metabolism
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Databases, Factual*
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Depsides
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Drug Design
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Electrophoresis, Polyacrylamide Gel
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HIV Integrase / metabolism
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HIV Integrase Inhibitors / chemistry*
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HIV Integrase Inhibitors / pharmacology
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HIV-1 / drug effects
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HIV-1 / enzymology*
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HIV-2 / enzymology
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Hydroxybenzoates / chemistry*
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Hydroxybenzoates / pharmacology*
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Lactones / chemistry
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Lactones / pharmacology*
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Lichens / chemistry
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Molecular Structure
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Oligodeoxyribonucleotides / chemistry
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Oligodeoxyribonucleotides / metabolism
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Structure-Activity Relationship
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Topoisomerase I Inhibitors
Substances
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Anti-HIV Agents
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Depsides
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HIV Integrase Inhibitors
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Hydroxybenzoates
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Lactones
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Oligodeoxyribonucleotides
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Topoisomerase I Inhibitors
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depsidone
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HIV Integrase
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DNA Topoisomerases, Type I