Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication

Antimicrob Agents Chemother. 1993 Aug;37(8):1659-64. doi: 10.1128/aac.37.8.1659.

Abstract

S-2720 [6-chloro-3,3-dimethyl-4-(isopropenyloxycarbonyl)-3,4- dihydroquinoxalin-2(1H)-thione], a quinoxaline derivative, was found to be a very potent inhibitor of both human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) activity and HIV-1 replication in tissue culture. Like other nonnucleoside RT inhibitors, S-2720 does not affect the HIV-2 RT. A S-2720-resistant virus was selected and shown to possess a mutation within the RT-coding region that has not previously been described. Notably, this mutation gives rise to a dramatic decrease in enzyme activity. S-2720, therefore, belongs to a new class of RT inhibitors that bind differently to the RT than other known nonnucleoside RT inhibitors. As no toxic effects were observed with S-2720 in mice, these quinoxaline derivatives deserve further evaluation to prove their potency as possible therapeutic agents for HIV-1 infection.

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood
  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / enzymology
  • Animals
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Cells, Cultured
  • Female
  • HIV Reverse Transcriptase
  • Lymphocytes / microbiology
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Quinoxalines / blood
  • Quinoxalines / pharmacokinetics
  • Quinoxalines / pharmacology*
  • RNA-Directed DNA Polymerase / genetics
  • Reverse Transcriptase Inhibitors*
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Quinoxalines
  • Reverse Transcriptase Inhibitors
  • S 2720
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase