Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae

Walter Balansa, Robiul Islam, Frank Fontaine, Andrew M. Piggott, Hua Zhang, Timothy I. Webb, Daniel F. Gilbert, Joseph W. Lynch, Robert J. Capon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Screening an extract library of >2500 southern Australian and Antarctic marine invertebrates and algae for modulators of glycine receptor (GlyR) chloride channels identified three Irciniidae sponges that yielded new examples of a rare class of glycinyl lactam sesterterpene, ircinialactam A, 8-hydroxyircinialactam A, 8-hydroxyircinialactam B, ircinialactam C, ent-ircinialactam C and ircinialactam D. Structure-activity relationship (SAR) investigations revealed a new pharmacophore with potent and subunit selective modulatory properties against α1 and α3 GlyR isoforms. Such GlyR modulators have potential application as pharmacological tools, and as leads for the development of GlyR targeting therapeutics to treat chronic inflammatory pain, epilepsy, spasticity and hyperekplexia.

Original languageEnglish
Pages (from-to)2912-2919
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number8
DOIs
Publication statusPublished - 15 Apr 2010
Externally publishedYes

Keywords

  • Glycine receptor (GlyR) chloride channels
  • Glycinyl lactam sesterterpenes
  • Irciniidae
  • Marine natural products

Fingerprint

Dive into the research topics of 'Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae'. Together they form a unique fingerprint.

Cite this