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 IC50S 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.
Rusconi, S., Cicero, M. L., Viganò, O., Sirianni, F., Bulgheroni, E., Ferramosca, S., … Galii, M. (2009). New macrocyclic amines showing activity as HIV entry inhibitors against wild type and multi-drug resistant viruses. In Molecules (Vol. 14, pp. 1927–1937). https://doi.org/10.3390/molecules14051927