Abstract
This discovered and optimized several novel HIV-1 fusion inhibitors and further evaluated the inhibitory activities of these compounds in vitro. Here, we have reported the computer-aided design, synthesis, and biological evaluation of a series of small molecule fusion inhibitors targeting HIV-1 gp41. Based on the structure of inhibitor (NB2), we carried out de novo design and screened out a series of novel structure molecules by using Leapfrog and Autodock programs. Our structure-based modification obtained a potent fusion inhibitor (IC₅₀ = 41.1 µg/mL). Several novel compounds were discovered as fusion inhibitors, which suggested that our design methodology is reliable, paving the way for de novo design of novel small-molecule HIV inhibitors targeting gp41.
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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Benzoates / chemical synthesis*
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Benzoates / chemistry
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Benzoates / pharmacology
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Computer-Aided Design*
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Drug Design
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Drug Evaluation, Preclinical
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HIV Envelope Protein gp41 / chemistry*
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HIV Fusion Inhibitors / chemical synthesis*
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HIV Fusion Inhibitors / chemistry
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HIV Fusion Inhibitors / pharmacology
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HIV Infections / drug therapy*
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HIV-1 / drug effects
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Humans
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Hydroxybenzoates
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Inhibitory Concentration 50
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Molecular Structure
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Molecular Targeted Therapy
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology
Substances
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4-(3-benzoyl-2-methyl-5-phenyl-1H-pyrrol-1-yl)-2-hydroxybenzoic Acid
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Anti-HIV Agents
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Benzoates
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HIV Envelope Protein gp41
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HIV Fusion Inhibitors
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Hydroxybenzoates
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Pyrroles