Balansa, Walter, Islam, Robi, Gilbert, Daniel, Fontaine, Frank, Xiao, Xue, Zhang, Hua, Piggott, Andrew M., Lynch, Joseph W., and Capon, Robert J. (2013) Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator. Bioorganic & Medicinal Chemistry, 21 (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.

Item ID:	65666
Item Type:	Article (Research - C1)
ISSN:	1464-3391
Copyright Information:	© 2013 Elsevier Ltd. All rights reserved.
Funders:	National Health and Medical Research Council of Australia (NHMRC), Australian Research Council (ARC)
Projects and Grants:	NHMRC #613448, ARC LP120100088
Date Deposited:	11 Jul 2024 04:26
FoR Codes:	03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030405 Molecular Medicine @ 30% 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060110 Receptors and Membrane Biology @ 50% 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 20%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 40% 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30% 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 30%
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