Identification of benzazole compounds that induce HIV-1 transcription

PLoS One. 2017 Jun 28;12(6):e0179100. doi: 10.1371/journal.pone.0179100. eCollection 2017.

Abstract

Despite advances in antiretroviral therapy, HIV-1 infection remains incurable in patients and continues to present a significant public health burden worldwide. While a number of factors contribute to persistent HIV-1 infection in patients, the presence of a stable, long-lived reservoir of latent provirus represents a significant hurdle in realizing an effective cure. One potential strategy to eliminate HIV-1 reservoirs in patients is reactivation of latent provirus with latency reversing agents in combination with antiretroviral therapy, a strategy termed "shock and kill". This strategy has shown limited clinical effectiveness thus far, potentially due to limitations of the few therapeutics currently available. We have identified a novel class of benzazole compounds effective at inducing HIV-1 expression in several cellular models. These compounds do not act via histone deacetylase inhibition or T cell activation, and show specificity in activating HIV-1 in vitro. Initial exploration of structure-activity relationships and pharmaceutical properties indicates that these compounds represent a potential scaffold for development of more potent HIV-1 latency reversing agents.

MeSH terms

  • Azoles / chemistry
  • Azoles / pharmacology*
  • Benzene / chemistry
  • Benzene / pharmacology*
  • Cell Line
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Transcription, Genetic / drug effects*

Substances

  • Azoles
  • Benzene