Abstract
Integracides, 4,4-dimethylergostane triterpenoids, are inhibitors of HIV-1 integrase, a critical enzyme in replication of HIV-1. The chemistry and structure-activity relationship of integracide B and related natural products are described. A charged group, e.g., a sulfate, carboxyl, or amino, is required for the HIV-1 integrase activity. These compounds showed HIV-1 integrase activity with IC(50) values in the range 4.8-15 muM and exhibited antiviral activity in a viral spread assay, but with only a small or no therapeutic window.
MeSH terms
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / isolation & purification*
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Anti-HIV Agents / pharmacology
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Combinatorial Chemistry Techniques
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HIV Integrase / metabolism*
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HIV Integrase Inhibitors / chemistry
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HIV Integrase Inhibitors / isolation & purification*
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HIV Integrase Inhibitors / pharmacology
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HIV-1 / drug effects
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Inhibitory Concentration 50
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Molecular Structure
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Structure-Activity Relationship
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Triterpenes / chemistry
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Triterpenes / isolation & purification*
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Triterpenes / pharmacology
Substances
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Anti-HIV Agents
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HIV Integrase Inhibitors
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Triterpenes
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integracide A
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integracide B
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HIV Integrase