title: Thiazolobenzimidazole: biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor.
abstract: Thiazolobenzimidazole (NSC 625487) was a highly potent inhibitor of human immunodeficiency virus-induced cell killing and viral replication in a variety of human cell lines, as well as fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2 and a pyridinone-resistant strain (A17) of HIV-1, a strain which is cross-resistant to several structurally diverse members of a common pharmacologic class of nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase but not HIV-2 reverse transcriptase. Combinations of thiazolobenzimidazole with either AZT or ddI synergistically inhibited HIV-1 induced cell killing in vitro. Thiazolobenzimidazole also inhibited the replication of the Rauscher murine leukemia retrovirus. Thus, thiazolobenzimidazole is a new active anti-HIV-1 chemotype and may represent a subclass of nonnucleoside reverse transcriptase inhibitors with an enhanced range of anti-retroviral activity.
authors.affiliation: Microbiology Research Department, Southern Research Institute, Birmingham, AL.
authors.forename: R W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: M G
authors.initials: MG
authors.lastname: Hollingshead
authors.forename: J
authors.initials: J
authors.lastname: Germany-Decker
authors.forename: E L
authors.initials: EL
authors.lastname: White
authors.forename: J B
authors.initials: JB
authors.lastname: McMahon
authors.forename: L B
authors.initials: LB
authors.lastname: Allen
authors.forename: L J
authors.initials: LJ
authors.lastname: Ross
authors.forename: W D
authors.initials: WD
authors.lastname: Decker
authors.forename: L
authors.initials: L
authors.lastname: Westbrook
authors.forename: W M
authors.initials: WM
authors.lastname: Shannon
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology*; D002460:Cell Line; D004277:DNA, Single-Stranded; D016049:Didanosine / Q000494:pharmacology; D004357:Drug Synergism; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000187:drug effects; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004277:DNA, Single-Stranded; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; C073244:1-(2',6'-difluorophenyl)-1H,3H-thiazolo(3,4-a)benzimidazole; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D016049:Didanosine