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;
2011-01-01

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.
2011
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].
File in questo prodotto:
File Dimensione Formato  
2011ChemMedChem_DDX3.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 923.84 kB
Formato Adobe PDF
923.84 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/11094
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo