Abstract
In continuation of our research efforts toward the identification and optimization for novel inhibitors of interaction between human immunodeficiency virus type 1 integrase and cellular cofactor LEDGF/p75, we designed and synthesized a new series of 4-benzylindole derivatives. Most of the title compounds proved to be able to block this protein-protein interaction (PPI), with a percentage ranging from 30% to 90% at 100 µM. The most promising derivative was compound 10b showing IC50 value of 6.41 µM. The main structure-activity relationships (SAR) are discussed and rationalized by docking studies.
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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Binding Sites
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HIV Integrase / metabolism*
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Intercellular Signaling Peptides and Proteins / metabolism*
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Molecular Docking Simulation
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Molecular Structure
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Protein Interaction Maps / drug effects*
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Protein Structure, Tertiary
Substances
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Anti-HIV Agents
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Indoles
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Intercellular Signaling Peptides and Proteins
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lens epithelium-derived growth factor
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HIV Integrase
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p31 integrase protein, Human immunodeficiency virus 1