Nobilamides A鈥揌, Long-Acting Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonists from Mollusk-Associated Bacteria
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- 作者：Zhenjian Lin ; Christopher A. Reilly ; Rowena Antemano ; Ronald W. Hughen ; Lenny Marett ; Gisela P. Concepcion ; Margo G. Haygood ; Baldomero M. Olivera ; Alan Light ; Eric W. Schmidt
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：June 9, 2011
- 年：2011
- 卷：54
- 期：11
- 页码：3746-3755
- 全文大小：938K
- 年卷期：v.54,no.11(June 9, 2011)
- ISSN：1520-4804
文摘
New compounds nobilamides A鈥揌 and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure鈥揳ctivity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogues for treatment of pain.