Abstract
Small molecules behaving as CD4 mimics were previously reported as HIV-1 entry inhibitors that block the gp120-CD4 interaction and induce a conformational change in gp120, exposing its co-receptor-binding site. A structure-activity relationship (SAR) study of a series of CD4 mimic analogs was conducted to investigate the contribution from the piperidine moiety of CD4 mimic 1 to anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. In addition, several hybrid molecules based on conjugation of a CD4 mimic analog with a selective CXCR4 antagonist were also synthesized and their utility evaluated.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Biomimetic Materials / chemistry*
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Biomimetic Materials / metabolism
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CD4 Antigens / chemistry
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CD4 Antigens / metabolism
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Cell Line
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HIV Envelope Protein gp120 / chemistry
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HIV Envelope Protein gp120 / metabolism
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HIV Fusion Inhibitors / chemical synthesis
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HIV Fusion Inhibitors / chemistry*
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HIV Fusion Inhibitors / toxicity
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Humans
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Piperidines / chemistry
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Protein Binding
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Receptors, CXCR4 / antagonists & inhibitors*
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Receptors, CXCR4 / metabolism
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Structure-Activity Relationship
Substances
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CD4 Antigens
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HIV Envelope Protein gp120
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HIV Fusion Inhibitors
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Piperidines
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Receptors, CXCR4
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gp120 protein, Human immunodeficiency virus 1
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piperidine