Molecules 2009, 14(5), 1927-1937; doi:10.3390/molecules14051927
Article

New Macrocyclic Amines Showing Activity as HIV Entry Inhibitors Against Wild Type and Multi-Drug Resistant Viruses

Stefano Rusconi 1,* email, Mirko Lo Cicero 1 , Ottavia Viganò 1 , Francesca Sirianni 1 , Elisabetta Bulgheroni 1 , Stefania Ferramosca 1 , Andrea Bencini 2 , Antonio Bianchi 2 , Lidia Ruiz 3 , Cecilia Cabrera 3 , Javier Martinez-Picado 3 email, Claudiu T. Supuran 2 email and Massimo Galli 1
1 Dipartimento di Scienze Cliniche “Luigi Sacco”, Sezione di Malattie Infettive e Immunopatologia, Università degli Studi, Ospedale Luigi Sacco, via G.B. Grassi 74, 20157 Milano, Italy 2 Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy 3 IrsiCaixa Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain
* Author to whom correspondence should be addressed.
Received: 2 April 2009; in revised form: 20 May 2009 / Accepted: 21 May 2009 / Published: 22 May 2009
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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 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.
Keywords: HIV-1; co-receptors; CXCR4; macrocyclic polyamines

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Cite This Article

MDPI and ACS Style

Rusconi, S.; Cicero, M.L.; Viganò, O.; Sirianni, F.; Bulgheroni, E.; Ferramosca, S.; Bencini, A.; Bianchi, A.; Ruiz, L.; Cabrera, C.; Martinez-Picado, J.; Supuran, C.T.; Galli, M. New Macrocyclic Amines Showing Activity as HIV Entry Inhibitors Against Wild Type and Multi-Drug Resistant Viruses. Molecules 2009, 14, 1927-1937.

AMA Style

Rusconi S, Cicero ML, Viganò O, Sirianni F, Bulgheroni E, Ferramosca S, Bencini A, Bianchi A, Ruiz L, Cabrera C, Martinez-Picado J, Supuran CT, Galli M. New Macrocyclic Amines Showing Activity as HIV Entry Inhibitors Against Wild Type and Multi-Drug Resistant Viruses. Molecules. 2009; 14(5):1927-1937.

Chicago/Turabian Style

Rusconi, Stefano; Cicero, Mirko Lo; Viganò, Ottavia; Sirianni, Francesca; Bulgheroni, Elisabetta; Ferramosca, Stefania; Bencini, Andrea; Bianchi, Antonio; Ruiz, Lidia; Cabrera, Cecilia; Martinez-Picado, Javier; Supuran, Claudiu T.; Galli, Massimo. 2009. "New Macrocyclic Amines Showing Activity as HIV Entry Inhibitors Against Wild Type and Multi-Drug Resistant Viruses." Molecules 14, no. 5: 1927-1937.

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