Abstract
Molecular modeling studies and an updated highly predictive 3-D QSAR model led to the discovery of exceptionally potent indolyl aryl sulfones (IASs) characterized by the presence of either a pyrrolidyn-2-one nucleus at the indole-2-carboxamide or some substituents at the indole-2-carbohydrazide. Compounds 7 and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166 cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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Cells, Cultured
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Drug Design
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Drug Resistance, Viral
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HIV-1 / drug effects*
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HIV-1 / genetics
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HIV-1 / isolation & purification
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Lymphocytes / drug effects
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Lymphocytes / virology
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Macrophages / drug effects
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Macrophages / virology
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Models, Molecular*
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Pyrrolidinones / chemistry
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Quantitative Structure-Activity Relationship
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Solubility
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Sulfones / chemical synthesis*
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Sulfones / chemistry
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Sulfones / pharmacology
Substances
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Anti-HIV Agents
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Indoles
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Pyrrolidinones
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Sulfones