Sesterterpenoids Isolated from the Sponge Phorbas sp. Activate Latent HIV-1 Provirus Expression

J Org Chem. 2016 Nov 18;81(22):11324-11334. doi: 10.1021/acs.joc.6b02312. Epub 2016 Nov 4.

Abstract

Eight new sesterterpenoids, alotaketals D (8) and E (9), ansellones D (10), E (11), F (12), and G (13), and anvilones A (14) and B (15), have been isolated from extracts of the marine sponge Phorbas sp. collected in Howe Sound British Columbia, and their structures have been elucidated by analysis of NMR and MS data. Ansellone F (12) contains a rare 1,2-3,4-bis-epoxydecalin substructure. Anvilones A (14) and B (15) have an unprecedented tetracylic anvilane terpenoid carbon skeleton. Using a cell culture model of latent HIV-1 infection, ansellone A (3), alotaketal D (8), and anvilone A (14) were found to induce HIV proviral gene expression similar to the control compound prostratin (1), while the known sesterterpenoid alotaketal C (2), isolated from the same extract, was more potent and gave a stronger response than prostratin (1). Like prostratin (1), all of the Phorbas sesterterpenoids with latency reversal agent properties appear to activate protein kinase C signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / virology
  • Cell Line
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Structure
  • Porifera / chemistry*
  • Proviruses / drug effects*
  • Proviruses / physiology
  • Sesterterpenes / chemistry
  • Sesterterpenes / isolation & purification*
  • Sesterterpenes / pharmacology
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Virus Activation / drug effects*
  • Virus Latency*

Substances

  • Sesterterpenes