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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

Fingerprint

HLA-A*33 antigen
Mollusca
Bacteria
Primary Cell Culture
Capsaicin
Spinal Ganglia
Binding Sites
Calcium
Pain
Pharmaceutical Preparations
vanilloid receptor subtype 1

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

Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria. / Lin, Zhenjian; Reilly, Christopher A.; Antemano, Rowena; Hughen, Ronald W.; Marett, Lenny; Concepcion, Gisela P.; Haygood, Margo; Olivera, Baldomero M.; Light, Alan; Schmidt, Eric W.

In: Journal of Medicinal Chemistry, Vol. 54, No. 11, 09.06.2011, p. 3746-3755.

Research output: Contribution to journalArticle

Lin, Z, Reilly, CA, Antemano, R, Hughen, RW, Marett, L, Concepcion, GP, Haygood, M, Olivera, BM, Light, A & Schmidt, EW 2011, 'Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria', Journal of Medicinal Chemistry, vol. 54, no. 11, pp. 3746-3755. https://doi.org/10.1021/jm101621u
Lin, Zhenjian ; Reilly, Christopher A. ; Antemano, Rowena ; Hughen, Ronald W. ; Marett, Lenny ; Concepcion, Gisela P. ; Haygood, Margo ; Olivera, Baldomero M. ; Light, Alan ; Schmidt, Eric W. / Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 11. pp. 3746-3755.
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