Title of article :
6-Aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays
Author/Authors :
Roberta Costi، نويسنده , , Roberto Di Santo، نويسنده , , Marino Artico، نويسنده , , Alessandra Roux، نويسنده , , Rino Ragno، نويسنده , , Silvio Massa، نويسنده , , Enzo Tramontano، نويسنده , , Massimiliano La Colla، نويسنده , , Roberta Loddo، نويسنده , , M.Elena Marongiu، نويسنده , , Alessandra Pani، نويسنده , , Paolo La Colla، نويسنده ,
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 (EC50=1.5 μM) and significant inhibition against rIN (strand transfer: IC50=7.9 μM; 3′-processing: IC50=7.0 μM). A preliminary molecular modeling study was carried out to compare the spatial conformation of 8a with those of L-731,988 (4) and 5CITEP (7) in the IN core.
Keywords :
Diketoacids , Pyrrole derivatives , Anti-HIV-1-IN agents , QSAR studies. , Aryldioxohexenoic acids
