title: New macrocyclic amines showing activity as HIV entry inhibitors against wild type and multi-drug resistant viruses.
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.
authors.affiliation: Dipartimento di Scienze Cliniche Luigi Sacco, Sezione di Malattie Infettive e Immunopatologia, Università degli Studi, Ospedale Luigi Sacco, Milano, Italy. stefano.rusconi@unimi.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.forename: Mirko
authors.initials: M
authors.lastname: Lo Cicero
authors.forename: Ottavia
authors.initials: O
authors.lastname: Viganò
authors.forename: Francesca
authors.initials: F
authors.lastname: Sirianni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bulgheroni
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferramosca
authors.forename: Andrea
authors.initials: A
authors.lastname: Bencini
authors.forename: Antonio
authors.initials: A
authors.lastname: Bianchi
authors.forename: Lidia
authors.initials: L
authors.lastname: Ruiz
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cabrera
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
mesh_terms: D000588:Amines / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001596:Benzylamines; D000080027:Cyclams; D018432:Drug Resistance, Multiple; D024882:Drug Resistance, Viral; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D010641:Phenotype; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors
chemical_list: D000588:Amines; D019380:Anti-HIV Agents; D001596:Benzylamines; D000080027:Cyclams; D023581:HIV Fusion Inhibitors; D006571:Heterocyclic Compounds; D011073:Polyamines; D019718:Receptors, CXCR4; C088327:plerixafor