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 Haygood, Baldomero M. Olivera, Alan Light, Eric W. Schmidt

26 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.

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Lin, Z., Reilly, C. A., Antemano, R., Hughen, R. W., Marett, L., Concepcion, G. P., ... Schmidt, E. W. (2011). Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria. Journal of Medicinal Chemistry, 54(11), 3746-3755. https://doi.org/10.1021/jm101621u