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2010 - Ircinialactams: subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae

icon pl  Patchliner publication in Bioorganic & Medical Chemistry (2010)

Authors: 
Balansa W, Islam R, Fontaine F, Piggott AM, Zhang H, Webb TI, Gilbert DF, Lynch JW, Capon RJ.

 

Journal: 
Bioorg Med Chem. (2010) 18(8):2912-9


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.


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