title: Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication.
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.
authors.affiliation: SBU Antiinfectives Research, Hoechst AG, Frankfurt, Germany.
authors.forename: J P
authors.initials: JP
authors.lastname: Kleim
authors.forename: R
authors.initials: R
authors.lastname: Bender
authors.forename: U M
authors.initials: UM
authors.lastname: Billhardt
authors.forename: C
authors.initials: C
authors.lastname: Meichsner
authors.forename: G
authors.initials: G
authors.lastname: Riess
authors.forename: M
authors.initials: M
authors.lastname: Rösner
authors.forename: I
authors.initials: I
authors.lastname: Winkler
authors.forename: A
authors.initials: A
authors.lastname: Paessens
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D054303:HIV Reverse Transcriptase; D008214:Lymphocytes / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011810:Quinoxalines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011810:Quinoxalines; D018894:Reverse Transcriptase Inhibitors; C083566:S 2720; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase