Title: Indolylarylsulfones bearing natural and unnatural amino acids. Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and Coxsackie B4 virus
Authors: Piscitelli, Francesco ×
Coluccia, Antonio
Brancale, Andrea
La Regina, Giuseppe
Sansone, Anna
Giordano, Cesare
Balzarini, Jan
Maga, Giovanni
Zanoli, Samantha
Samuele, Alberta
Cirilli, Roberto
La Torre, Francesco
Lavecchia, Antonio
Novellino, Ettore
Silvestri, Romano #
Issue Date: Apr-2009
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:52 issue:7 pages:1922-1934
Abstract: New potent indolylarylsulfone (IAS) HIV-I NNRTIs were obtained by coupling natural and unnatural amino acids to the 2-carboxamide and introducing different electron-withdrawing substituents at position 4 and 5 of the indole nucleus. The new IASs inhibited the HIV-1 replication in human T-lymphocyte (CEM) cells at low/subnanomolar concentration and were weakly cytostatic. Against the mutant L100I, K103N, and Y181C RT HIV-1 strains in CEM cells, sulfones 3, 4, 19, 27, and 31 were comparable to EFV. The new IASs were inhibitors to Coxsackie B4 virus at low micromolar (2-9 mu M) concentrations. Superimposition of PLANTS docked conformations of IASs 19 and 9 revealed different hydrophobic interactions of the 3,5-dimethylphenyl group, for which a staking interaction with Tyr181 aromatic side chain was observed. The binding mode of 19 was not affected by the L100I mutation and was consistent with the interactions reported for the WT strain.
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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