Abstract
A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 microM as an inhibitor of the cytopathic effect of HIV-1RF in CEM-SS cells, which represents a significant increase in potency over cosalane itself (EC50 5.1 microM). Both cosalane and the new analog are inhibitors of viral entry into target cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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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Aurintricarboxylic Acid / analogs & derivatives*
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Aurintricarboxylic Acid / chemical synthesis*
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Aurintricarboxylic Acid / chemistry
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Aurintricarboxylic Acid / pharmacology
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CD4 Antigens / chemistry
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CD4 Antigens / drug effects
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Drug Design
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HIV-1 / drug effects*
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HIV-1 / growth & development
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Humans
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Models, Molecular
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Molecular Conformation
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Molecular Structure
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Protein Conformation
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Anti-HIV Agents
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CD4 Antigens
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cosalane
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Aurintricarboxylic Acid