Abstract
Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (∼40 nM for wild-type PR and 100 nM for ANAM-11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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HIV Infections / drug therapy*
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HIV Protease / chemistry*
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HIV Protease / classification
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HIV Protease / genetics
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HIV Protease Inhibitors / chemistry
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HIV Protease Inhibitors / pharmacology
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HIV Protease Inhibitors / therapeutic use*
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Hydrophobic and Hydrophilic Interactions
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Inhibitory Concentration 50
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Molecular Mimicry
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Mutation / drug effects*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology
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Naphthalenes / therapeutic use
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Protein Binding / drug effects
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Protein Multimerization / drug effects*
Substances
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HIV Protease Inhibitors
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Naphthalenes
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HIV Protease