Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae
Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae
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DOI：
10.1016/j.bmc.2010.03.002
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发表时间：
2010-04-15
影响因子：
3.5
通讯作者：
Capon, Robert J.
中科院分区：
文献类型：
--
作者：
Balansa, Walter;Islam, Robiul;Capon, Robert J.
对>2500种澳大利亚南部和南极海洋无脊椎动物和藻类的提取物文库进行甘氨酸受体（GlyR）氯化物通道调节剂的筛选，鉴定了三种Irciniidae海绵，其产生了一类罕见的甘氨酰内酰胺二萜的新实例：ircinialactam A、8-羟基ircinialactam A、8-羟基ircinialactam B、ircinialactam C、ent-ircinialactam C和ircinialactam D。构效关系（SAR）研究揭示了一种新的药效团，对α 1和α 3 GlyR亚型具有强效和亚基选择性调节特性。此类GlyR调节剂具有作为药理学工具的潜在应用，并且作为开发GlyR靶向治疗剂以治疗慢性炎性疼痛、癫痫、痉挛和过度兴奋的先导。(C)2010爱思唯尔有限公司保留所有权利。
Screening an extract library of >2500 southern Australian and Antarctic marine invertebrates and algae for modulators of glycine receptor ( GlyR) chloride channels identified three Irciniidae sponges that yielded new examples of a rare class of glycinyl lactam sesterterpene, ircinialactam A,8-hydroxyircinialactam A, 8-hydroxyircinialactam B, ircinialactam C, ent-ircinialactam C and ircinialactam D. Structure-activity relationship (SAR) investigations revealed a new pharmacophore with potent and subunit selective modulatory properties against alpha 1 and alpha 3 GlyR isoforms. Such GlyR modulators have potential application as pharmacological tools, and as leads for the development of GlyR targeting therapeutics to treat chronic inflammatory pain, epilepsy, spasticity and hyperekplexia. (C) 2010 Elsevier Ltd. All rights reserved.