Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator

Md Islam, Walter Balansa, Daniel F Gilbert, Frank Fortaine, Xue Xiao, Hua Zhang, Andrew M Piggott, Joseph W Lynch, Robert J Capon

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Chemical analysis of a specimen of the sponge Ianthella cf. flabelliformis returned two new sesquiterpene glycinyl lactams, ianthellalactams A (1) and B (2), the known sponge sesquiterpene dictyodendrillin (3) and its ethanolysis artifact ethyl dictyodendrillin (4), and five known sponge indole alkaloids, aplysinopsin (5), 8E-3′-deimino-3′-oxoaplysinopsin (6), 8Z-3′-deimino-3′-oxoaplysinopsin (7), dihydroaplysinopsin (8) and tubastrindole B (9). The equilibrated mixture 6/7 exhibited glycine-gated chloride channel receptor (GlyR) antagonist activity with a bias towards α3 over α1 GlyR, while tubastrindole B (9) exhibited a bias towards α1 over α3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of α1 GlyR, with no effect on α3 GlyR—a pharmacology that could prove useful in the treatment of movement disorders such as spasticity and hyperekplexia. Our investigations into the GlyR modulatory properties of 1–9 were further supported by the synthesis of a number of structurally related indole alkaloids.
Original languageEnglish
Pages (from-to)4420-4425
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number14
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Indole Alkaloids
Chloride Channels
Sesquiterpenes
Porifera
Alkaloids
Glycine
Modulators
Lactams
Movement Disorders
Artifacts
Chemical analysis
Pharmacology
tubastrindole B
aplysinopsin

Cite this

Islam, Md ; Balansa, Walter ; Gilbert, Daniel F ; Fortaine, Frank ; Xiao, Xue ; Zhang, Hua ; Piggott, Andrew M ; Lynch, Joseph W ; Capon, Robert J. / Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 14. pp. 4420-4425.
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abstract = "Chemical analysis of a specimen of the sponge Ianthella cf. flabelliformis returned two new sesquiterpene glycinyl lactams, ianthellalactams A (1) and B (2), the known sponge sesquiterpene dictyodendrillin (3) and its ethanolysis artifact ethyl dictyodendrillin (4), and five known sponge indole alkaloids, aplysinopsin (5), 8E-3′-deimino-3′-oxoaplysinopsin (6), 8Z-3′-deimino-3′-oxoaplysinopsin (7), dihydroaplysinopsin (8) and tubastrindole B (9). The equilibrated mixture 6/7 exhibited glycine-gated chloride channel receptor (GlyR) antagonist activity with a bias towards α3 over α1 GlyR, while tubastrindole B (9) exhibited a bias towards α1 over α3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of α1 GlyR, with no effect on α3 GlyR—a pharmacology that could prove useful in the treatment of movement disorders such as spasticity and hyperekplexia. Our investigations into the GlyR modulatory properties of 1–9 were further supported by the synthesis of a number of structurally related indole alkaloids.",
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Islam, M, Balansa, W, Gilbert, DF, Fortaine, F, Xiao, X, Zhang, H, Piggott, AM, Lynch, JW & Capon, RJ 2013, 'Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator', Bioorganic and Medicinal Chemistry, vol. 21, no. 14, pp. 4420-4425. https://doi.org/10.1016/j.bmc.2013.04.061

Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator. / Islam, Md; Balansa, Walter; Gilbert, Daniel F; Fortaine, Frank ; Xiao, Xue ; Zhang, Hua; Piggott, Andrew M; Lynch, Joseph W; Capon, Robert J.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 14, 2013, p. 4420-4425.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator

AU - Islam, Md

AU - Balansa, Walter

AU - Gilbert, Daniel F

AU - Fortaine, Frank

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AU - Piggott, Andrew M

AU - Lynch, Joseph W

AU - Capon, Robert J

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