New iantherans from the marine sponge Ianthella quadrangulata: novel agonists of the P2Y(11) receptor

J Med Chem. 2007 Nov 15;50(23):5600-7. doi: 10.1021/jm070043r. Epub 2007 Oct 17.

Abstract

Three new iantherans, iso-iantheran A (1), 8-carboxy-iso-iantheran A (2), and iso-iantheran B (4) were isolated together with two further new brominated tyrosine-derived metabolites 5 and 6 from the polar extract of the Australian marine sponge Ianthella quadrangulata. Structures were elucidated on the basis of extensive spectral analysis. The dimeric benzofuran skeleton including a 2,3-dihydroxy-1,3-butadiene disulfate moiety found in 1, 2, and 4 is a unique feature of iantherans and to date only described for iantherans A and B. Iso-iantheran A (1) and 8-carboxy-iso-iantheran A (2) exhibited agonist activity at P2Y11 receptors with EC50 values of 1.29 muM and 0.48 muM, respectively. Compound 2 showed some selectivity for P2Y11 over P2Y1 and P2Y2 receptors. Compounds 1 and 2 represent a new structural type for the development of P2Y11 receptor agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans / chemistry
  • Benzofurans / isolation & purification*
  • Benzofurans / pharmacology
  • Calcium / metabolism
  • Cell Line, Tumor
  • Humans
  • Ligands
  • Models, Molecular
  • Porifera / chemistry*
  • Purinergic P2 Receptor Agonists*
  • Receptors, Purinergic P2
  • Structure-Activity Relationship
  • Sulfuric Acid Esters / chemistry
  • Sulfuric Acid Esters / isolation & purification*
  • Sulfuric Acid Esters / pharmacology
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry
  • Tyrosine / isolation & purification*
  • Tyrosine / pharmacology

Substances

  • 8-carboxy-iso-iantheran A
  • Benzofurans
  • Ligands
  • P2RY11 protein, human
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2
  • Sulfuric Acid Esters
  • iso-iantheran A
  • iso-iantheran B
  • Tyrosine
  • Calcium