TY - JOUR
T1 - Ircinialactams
T2 - Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae
AU - Balansa, Walter
AU - Islam, Robiul
AU - Fontaine, Frank
AU - Piggott, Andrew M.
AU - Zhang, Hua
AU - Webb, Timothy I.
AU - Gilbert, Daniel F.
AU - Lynch, Joseph W.
AU - Capon, Robert J.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - 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.
AB - 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.
KW - Glycine receptor (GlyR) chloride channels
KW - Glycinyl lactam sesterterpenes
KW - Irciniidae
KW - Marine natural products
UR - http://www.scopus.com/inward/record.url?scp=77950519951&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2010.03.002
DO - 10.1016/j.bmc.2010.03.002
M3 - Article
C2 - 20346682
AN - SCOPUS:77950519951
VL - 18
SP - 2912
EP - 2919
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 8
ER -