Study of marine natural products including resorcyclic acid lactones from Humicola fuscoatra that reactivate latent HIV-1 expression in an in vitro model of central memory CD4+ T cells

J Nat Prod. 2014 Mar 28;77(3):618-24. doi: 10.1021/np400889x. Epub 2014 Feb 4.

Abstract

An extract of Humicola fuscoatra (UCSC strain no. 108111A) was shown to reactivate latent HIV-1 expression in an in vitro model of central memory CD4+ T cells. We report the bioassay-guided isolation and structure determination of several resorcyclic acid lactones, including four known compounds, radicicol (1, aka. monorden) and pochonins B (2), C (3), and N (4), and three new analogues, radicicols B-D (5-7). Compounds 1-3 and 5 showed moderate activities in the memory T cell model of HIV-1 latency. Radicicol (1) displayed lower potency in reactivating latent HIV-1 (EC50 = 9.1 μM) relative to the HDAC inhibitors apicidin (EC50 = 0.3 μM), romidepsin (EC50 = 0.003 μM), and SAHA (EC50 = 0.6 μM); however, it achieved equivalent maximum efficacy relative to the positive control compounds (98% of SAHA and romidepsin).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Ascomycota / chemistry*
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • CD4-Positive T-Lymphocytes / virology*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Lactones / chemistry*
  • Lactones / pharmacology
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Marine Biology
  • Models, Biological
  • Molecular Structure
  • Virus Latency / drug effects

Substances

  • Biological Products
  • Histone Deacetylase Inhibitors
  • Lactones
  • Macrolides
  • monorden