6-aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays.
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.
Costi
Roberta
R
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.
Di Santo
Roberto
R
Artico
Marino
M
Roux
Alessandra
A
Ragno
Rino
R
Massa
Silvio
S
Tramontano
Enzo
E
La Colla
Massimiliano
M
Loddo
Roberta
R
Marongiu
M Elena
ME
Pani
Alessandra
A
La Colla
Paolo
P
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*
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors