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Updated: Jun 22, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
New macrocyclic amines showing activity as HIV entry inhibitors against wild type and multi-drug resistant viruses
Stefano Rusconi1, Mirko Lo Cicero, Ottavia Viganò
1Dipartimento di Scienze Cliniche Luigi Sacco, Sezione di Malattie Infettive e Immunopatologia, Università degli Studi, Ospedale Luigi Sacco, Milano, Italy. stefano.rusconi@unimi.it
Abstract:
Considering as a lead molecule the chemokine CXCR4 receptor antagonist AMD-3100, which shows significant anti-HIV activity in vitro and in vivo, we investigated a series of structurally related macrocyclic polyamines incorporating o,o'-phenanthroline or 2,2'-bipyridyl scaffolds as potential antiviral agents with lower toxicity and increased activity against both wild type X4-tropic and dual tropic HIV strains. The antiviral activity of these compounds was evaluated by susceptibility assays in PBMC (Peripheral Blood Mononuclear Cells) and compared to that of AMD-3100. The newly investigated compounds showed IC(50)s values in the low micromolar range and significantly inhibited the viral replication of wild type X4-tropic isolate and dual tropic strains. These macrocyclic polyamines constitute a promising class of HIV entry inhibitors.
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