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.
Original language | English |
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Pages (from-to) | 1371-1389 |
Number of pages | 19 |
Journal | ChemMedChem |
Volume | 6 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 1 2011 |
Keywords
- Antiviral agents
- DDX3
- Helicase
- HIV-1
- Host cofactors
- Inhibitors
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Organic Chemistry
- Molecular Medicine