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

Eur J Med Chem. 2014 Jun 10:80:101-11. doi: 10.1016/j.ejmech.2014.04.027. Epub 2014 Apr 12.


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.

Keywords: AIDS; HIV-1; Indolylarylsulfone; Nonnucleoside inhibitor; Reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Drug Design
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / chemistry
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • Humans
  • Indoles / chemistry*
  • Inhibitory Concentration 50
  • Models, Molecular
  • Protein Conformation
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis
  • Sulfones / chemistry*
  • Sulfones / pharmacology*


  • Indoles
  • Reverse Transcriptase Inhibitors
  • Sulfones
  • indole
  • HIV Reverse Transcriptase