Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria

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

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

New compounds nobilamides A-H 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-activity 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.

Original languageEnglish (US)
Pages (from-to)3746-3755
Number of pages10
JournalJournal of Medicinal Chemistry
Volume54
Issue number11
DOIs
StatePublished - Jun 9 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria'. Together they form a unique fingerprint.

Cite this