A hit optimization protocol applied to the first nonnucleoside inhibitor of the ATPase activity of human DEAD-box RNA helicase DDX3 led to the design and synthesis of second-generation rhodanine derivatives with better inhibitory activity toward cellular DDX3 and HIV-1 replication. Additional DDX3 inhibitors were identified among triazine compounds. Biological data were rationalized in terms of structure-activity relationships and docking simulations. Antiviral activity and cytotoxicity of selected DDX3 inhibitors are reported and discussed. A thorough analysis confirmed human DDX3 as a valid anti-HIV target. The compounds described herein represent a significant advance in the pursuit of novel drugs that target HIV-1 host cofactors.

Maga, G., Falchi, F., Botta, M., Botta, L., Casaluce, G., Bernardini, M., et al. (2011). Toward the Discovery of Novel Anti-HIV Drugs. Second Generation Inhibitors of the Cellular ATPase DDX3 with Improved Anti-HIV Activity: Synthesis, Structure-Activity Relationship Analysis, Cytotoxicity Studies, and Target Validation. CHEMMEDCHEM, 6(8), 1371-1389 [10.1002/cmdc.201100166].

Toward the Discovery of Novel Anti-HIV Drugs. Second Generation Inhibitors of the Cellular ATPase DDX3 with Improved Anti-HIV Activity: Synthesis, Structure-Activity Relationship Analysis, Cytotoxicity Studies, and Target Validation.

BOTTA, MAURIZIO;MANETTI, FABRIZIO;
2011

Abstract

A hit optimization protocol applied to the first nonnucleoside inhibitor of the ATPase activity of human DEAD-box RNA helicase DDX3 led to the design and synthesis of second-generation rhodanine derivatives with better inhibitory activity toward cellular DDX3 and HIV-1 replication. Additional DDX3 inhibitors were identified among triazine compounds. Biological data were rationalized in terms of structure-activity relationships and docking simulations. Antiviral activity and cytotoxicity of selected DDX3 inhibitors are reported and discussed. A thorough analysis confirmed human DDX3 as a valid anti-HIV target. The compounds described herein represent a significant advance in the pursuit of novel drugs that target HIV-1 host cofactors.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/11094
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