Abstract
A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / pharmacology
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Betulinic Acid
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Enzyme Inhibitors / pharmacology
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HIV-1 / drug effects*
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HIV-2 / drug effects
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Humans
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Models, Molecular
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Molecular Structure
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Pentacyclic Triterpenes
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
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Triterpenes / chemical synthesis*
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Triterpenes / chemistry
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Triterpenes / pharmacology*
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Tumor Cells, Cultured
Substances
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Antiviral Agents
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Enzyme Inhibitors
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N-(3,30-dihydroxylup-20(29)-en-28-oyl)-11-aminoundecanoic acid
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N-(3-hydroxy-30-((2'-hydroxyethyl)thio)lup-20(29)-en-28-oyl)-11-aminoundecanoic acid
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Pentacyclic Triterpenes
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Reverse Transcriptase Inhibitors
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Triterpenes
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betulinylaminoundecanoic acid
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Betulinic Acid