Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. Here we describe the identification of the first small molecules specifically designed to inhibit the HIV-1 replication by targeting the RNA binding site of the human DEAD-Box RNA helicase DDX3. Optimization of a easily synthetically accessible hit (1) identified by application of a high-throughput docking approach afforded the promising compounds 6 and 8 which proved to inhibit both the helicase and ATPase activity of DDX3 and to reduce the viral load of peripheral blood mononuclear cells (PBMC) infected with HIV-1.

Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: Towards the next generation HIV-1 inhibitors / Radi, Marco; Federico, Falchi; Anna, Garbelli; Alberta, Samuele; Vincenzo, Bernardo; Stefania, Paolucci; Fausto, Baldanti; Silvia, Schenone; Fabrizio, Manetti; Giovanni, Maga; Maurizio, Botta. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 22:(2012), pp. 2094-2098. [10.1016/j.bmcl.2011.12.135]

Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: Towards the next generation HIV-1 inhibitors

RADI, Marco;
2012-01-01

Abstract

Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. Here we describe the identification of the first small molecules specifically designed to inhibit the HIV-1 replication by targeting the RNA binding site of the human DEAD-Box RNA helicase DDX3. Optimization of a easily synthetically accessible hit (1) identified by application of a high-throughput docking approach afforded the promising compounds 6 and 8 which proved to inhibit both the helicase and ATPase activity of DDX3 and to reduce the viral load of peripheral blood mononuclear cells (PBMC) infected with HIV-1.
2012
Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: Towards the next generation HIV-1 inhibitors / Radi, Marco; Federico, Falchi; Anna, Garbelli; Alberta, Samuele; Vincenzo, Bernardo; Stefania, Paolucci; Fausto, Baldanti; Silvia, Schenone; Fabrizio, Manetti; Giovanni, Maga; Maurizio, Botta. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 22:(2012), pp. 2094-2098. [10.1016/j.bmcl.2011.12.135]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2393541
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