6-aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays

Roberta Costi; Roberto Di Santo; Marino Artico; Alessandra Roux; Rino Ragno; Silvio Massa; Enzo Tramontano; Massimiliano La Colla; Roberta Loddo; M Elena Marongiu; Alessandra Pani; Paolo La Colla

doi:10.1016/j.bmcl.2004.01.037

6-aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1745-9. doi: 10.1016/j.bmcl.2004.01.037.

Authors

Roberta Costi¹, Roberto Di Santo, Marino Artico, Alessandra Roux, Rino Ragno, Silvio Massa, Enzo Tramontano, Massimiliano La Colla, Roberta Loddo, M Elena Marongiu, Alessandra Pani, Paolo La Colla

Affiliation

¹ 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.

PMID: 15026063
DOI: 10.1016/j.bmcl.2004.01.037

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology*
Cell Survival / drug effects
Cell Survival / physiology
HIV Integrase Inhibitors / chemistry*
HIV Integrase Inhibitors / pharmacology*
HIV-1 / drug effects*
HIV-1 / enzymology*
HIV-1 / physiology
Virus Replication / drug effects*

Substances

Anti-HIV Agents
HIV Integrase Inhibitors