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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, V.
La Regina, G.
Coluccia, A.
Pelliccia, S.
Brancale, A.
Maga, G.
Crespan, E.
Badia, R.
Riveira Muñoz, E.
Esté, J. A.
Ferretti, R.
Cirilli, R.
Zamperini, Claudio
Botta, Maurizio 
Schols, D.
Limongelli, V.
Agostino, B.
Novellino, E.
Silvestri, R.
Issue Date: 2014
Project: None 
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.
ISSN: 0022-2623
DOI: 10.1021/jm5011622
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