Thiazolobenzimidazole: biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor

  • Antiviral Res. 1993 Jul;21(3):247-65. doi: 10.1016/0166-3542(93)90031-d.
R W Buckheit Jr  1 ,  M G Hollingshead ,  J Germany-Decker ,  E L White ,  J B McMahon ,  L B Allen ,  L J Ross ,  W D Decker ,  L Westbrook ,  W M Shannon
Affiliations
  • 1. Microbiology Research Department, Southern Research Institute, Birmingham, AL.
PMID: 7692815 DOI: 10.1016/0166-3542(93)90031-d
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.

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