期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 21, 期 14, 页码 4420-4425出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.04.061
关键词
Glycine-gated chloride channel receptor modulators; Sesterterpene tetronic acid glycinyl lactams lanthella cf. flabelliformis; Marine natural products chemistry
资金
- Australian Development Scholarship
- University of Queensland Scholarship
- Institute for Molecular Bioscience
- Queensland Brain Institute
- University of Queensland
- National Health and Medical Research Council [613448]
- Australian Research Council [LP120100088]
- Australian Research Council [LP120100088] Funding Source: Australian Research Council
Chemical analysis of a specimen of the sponge lanthella 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 alpha 3 over alpha 1 GlyR, while tubastrindole B (9) exhibited a bias towards alpha 1 over alpha 3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of alpha 1 GlyR, with no effect on alpha 3 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. (C) 2013 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据