文摘
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¡ä-deimino-3¡ä-oxoaplysinopsin (6), 8Z-3¡ä-deimino-3¡ä-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 ¦Á3 over ¦Á1 GlyR, while tubastrindole B (9) exhibited a bias towards ¦Á1 over ¦Á3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of ¦Á1 GlyR, with no effect on ¦Á3 GlyR¡ªa 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.