New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors

Valeria Famiglini, Giuseppe La Regina, Antonio Coluccia, Sveva Pelliccia, Andrea Brancale, Giovanni Maga, Emmanuele Crespan, Roger Badia, Bonaventura Clotet, José A. Esté, Roberto Cirilli, Ettore Novellino, Romano Silvestri

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences. © 2014 Elsevier Masson SAS. All rights reserved.
Original languageEnglish
Pages (from-to)101-111
JournalEuropean Journal of Medicinal Chemistry
Volume80
DOIs
Publication statusPublished - 10 Jun 2014

Keywords

  • AIDS
  • HIV-1
  • Indolylarylsulfone
  • Nonnucleoside inhibitor
  • Reverse transcriptase

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