Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 4420-4425 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 21 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 2013 |
| Externally published | Yes |
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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 journal › Article › Research › peer-review
TY - JOUR
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
AU - Xiao, Xue
AU - Zhang, Hua
AU - Piggott, Andrew M
AU - Lynch, Joseph W
AU - Capon, Robert J
N1 - During the time of this publication, the author was not affiliated with CDU
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84879008046&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2013.04.061
DO - 10.1016/j.bmc.2013.04.061
M3 - Article
VL - 21
SP - 4420
EP - 4425
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 14
ER -