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Title: Indolylarylsulfones carrying a heterocyclic tail as very potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors
Authors: Famiglini, Valeria ×
La Regina, Giuseppe
Coluccia, Antonio
Pelliccia, Sveva
Brancale, Andrea
Maga, Giovanni
Crespan, Emmanuele
Badia, Roger
Riveira-Muñoz, Eva
Esté, José A
Ferretti, Rosella
Cirilli, Roberto
Zamperini, Claudio
Botta, Maurizio
Schols, Dominique
Limongelli, Vittorio
Agostino, Bruno
Novellino, Ettore
Silvestri, Romano #
Issue Date: Dec-2014
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:57 issue:23 pages:9945-57
Article number: 10.1021/jm5011622
Abstract: We synthesized new indolylarylsulfone (IAS) derivatives carrying a heterocyclic tail at the indole-2-carboxamide nitrogen as potential anti-HIV/AIDS agents. Several new IASs yielded EC50 values <1.0 nM against HIV-1 WT and mutant strains in MT-4 cells. The (R)-11 enantiomer proved to be exceptionally potent against the whole viral panel; in the reverse transcriptase (RT) screening assay, it was remarkably superior to NVP and EFV and comparable to ETV. The binding poses were consistent with the one previously described for the IAS non-nucleoside reverse transcriptase inhibitors. Docking studies showed that the methyl group of (R)-11 points toward the cleft created by the K103N mutation, different from the corresponding group of (S)-11. By calculating the solvent-accessible surface, we observed that the exposed area of RT in complex with (S)-11 was larger than the area of the (R)-11 complex. Compounds 6 and 16 and enantiomer (R)-11 represent novel robust lead compounds of the IAS class.
URI: 
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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