Abstract
A series of N-aryl-naphthylamines, exemplified by the structures 11-16, were chosen for an in-house library screening to assay their ability to disrupt the interaction between the LEDGF cofactor and the HIV integrase. Structure modification led also to design and synthesize new compounds 17a-f. Compounds 11e,h,k,n, 13b, and 14 showed good activity in AlphaScreen assay. The most active compound 11e (IC50 = 2.5 μM) was selected for molecular modeling studies and showed a binding mode similar to the one of the known LEDGIN 8.
Keywords:
Integrase; LEDGF/p75; LEDGINs; N-aryl-naphthylamine.
Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Naphthylamine / analogs & derivatives*
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1-Naphthylamine / chemical synthesis
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1-Naphthylamine / chemistry
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1-Naphthylamine / pharmacology
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Dose-Response Relationship, Drug
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Drug Discovery*
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HIV Integrase / metabolism*
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HIV Integrase Inhibitors / chemical synthesis
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HIV Integrase Inhibitors / chemistry
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HIV Integrase Inhibitors / pharmacology*
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Humans
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Intercellular Signaling Peptides and Proteins / metabolism*
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Models, Molecular
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Molecular Structure
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Protein Binding / drug effects
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Structure-Activity Relationship
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Tumor Cells, Cultured
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para-Aminobenzoates / chemical synthesis
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para-Aminobenzoates / chemistry
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para-Aminobenzoates / pharmacology*
Substances
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HIV Integrase Inhibitors
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Intercellular Signaling Peptides and Proteins
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lens epithelium-derived growth factor
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para-Aminobenzoates
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1-Naphthylamine
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HIV Integrase