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

doi:10.1016/j.bmc.2010.03.002

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 journal › Article › peer-review

52 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 language	English
Pages (from-to)	2912-2919
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2010.03.002
Publication status	Published - 15 Apr 2010
Externally published	Yes

Keywords

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

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10.1016/j.bmc.2010.03.002

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title = "Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae",

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.",

keywords = "Glycine receptor (GlyR) chloride channels, Glycinyl lactam sesterterpenes, Irciniidae, Marine natural products",

author = "Walter Balansa and Robiul Islam and Frank Fontaine and Piggott, {Andrew M.} and Hua Zhang and Webb, {Timothy I.} and Gilbert, {Daniel F.} and Lynch, {Joseph W.} and Capon, {Robert J.}",

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doi = "10.1016/j.bmc.2010.03.002",

language = "English",

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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

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JO - Bioorganic and Medicinal Chemistry

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IS - 8

ER -

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

Abstract

Keywords

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