title: 6-aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays.
abstract: A series of 6-aryl-2,4-dioxo-5-hexenoic acids, were synthesized and tested against HIV-1 in cell-based assays and against recombinant HIV-1 integrase (rIN) in enzyme assays. Compound 8a showed potent antiretroviral activity (EC(50)=1.5 microM) and significant inhibition against rIN (strand transfer: IC(50)=7.9 microM; 3'-processing: IC(50)=7.0 microM). A preliminary molecular modeling study was carried out to compare the spatial conformation of 8a with those of L-731988 (4) and 5CITEP (7) in the IN core.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università degli Studi di Roma 'La Sapienza', P. le A. Moro 5, I-00185 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Costi
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: Alessandra
authors.initials: A
authors.lastname: Roux
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.forename: Silvio
authors.initials: S
authors.lastname: Massa
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
authors.forename: Massimiliano
authors.initials: M
authors.lastname: La Colla
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.forename: M Elena
authors.initials: ME
authors.lastname: Marongiu
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pani
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors