Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 May 22;14(5):1927-37.
doi: 10.3390/molecules14051927.

New macrocyclic amines showing activity as HIV entry inhibitors against wild type and multi-drug resistant viruses

Stefano Rusconi  1 , Mirko Lo Cicero, Ottavia Viganò, Francesca Sirianni, Elisabetta Bulgheroni, Stefania Ferramosca, Andrea Bencini, Antonio Bianchi, Lidia Ruiz, Cecilia Cabrera, Javier Martinez-Picado, Claudiu T Supuran, Massimo Galli
Affiliations

New macrocyclic amines showing activity as HIV entry inhibitors against wild type and multi-drug resistant viruses

Stefano Rusconi et al. Molecules. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
AMD3100 and related compounds plus the four newly synthesized macrocyclic polyamines.
Scheme 1
Scheme 1
Synthetic procedures for compounds 8 and 9.
Scheme 2
Scheme 2
Synthetic procedure used for compound 7.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. UNAIDS/WHO. AIDS Epidemic Update: December 2008. Available online: http://www.unaids.org.
    1. Graves M.C., Lim J.J., Heimer E.P., Kramer R.A. An 11-kDa form of human immunodeficiency virus protease expressed in Escherichia coli is sufficient for enzymatic activity. Proc. Natl. Acad. Sci. USA. 1988;85:2449–2453. - PMC - PubMed
    1. Drake S.M. NNRTIs-a new class of drugs for HIV. J. Antimicr. Chemother. 2000;45:417–420. doi: 10.1093/jac/45.4.417. - DOI - PubMed
    1. De Clercq E. New approaches toward anti-HIV chemotherapy. J. Med. Chem. 2005;48:1297–1313. doi: 10.1021/jm040158k. - DOI - PubMed
    1. Barbaro G., Scozzafava A., Mastrolorenzo A., Supuran C.T. Highly active antiretroviral therapy: current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome. Curr. Pharm. Des. 2005;11:1805–1843. doi: 10.2174/1381612053764869. - DOI - PubMed

Publication types

MeSH terms