Synthesis and preliminary biological evaluation of truncated zoanthenol analogues

Bioorg Med Chem Lett. 2004 May 17;14(10):2647-51. doi: 10.1016/j.bmcl.2004.02.064.

Abstract

Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique structural element. In this report, we designed and synthesized ABC-ring 6 and CDEFG-ring 7, which are truncated analogues of the northern and southern hemispheres of zoanthenol 5, respectively, and which incorporate all of the functionality of each hemisphere. A preliminary SAR study suggested that the hydrochloride of the CEFG-ring portion is an active pharmacophore for suppressing the growth of interleukin-6-dependent MH60 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / pharmacology
  • Animals
  • Cell Proliferation / drug effects
  • Cnidaria / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Heterocyclic Compounds, Bridged-Ring / chemical synthesis
  • Heterocyclic Compounds, Bridged-Ring / pharmacology*
  • Hybridomas
  • Interleukin-6 / antagonists & inhibitors
  • Mice
  • Molecular Mimicry
  • Osteoporosis / drug therapy
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Heterocyclic Compounds, Bridged-Ring
  • Interleukin-6
  • zoanthenol