LAT Transport Inhibitors from Pittosporum venulosum Identified by NMR Fingerprint Analysis

J Nat Prod. 2015 Jun 26;78(6):1215-20. doi: 10.1021/np500968t. Epub 2015 May 18.

Abstract

(1)H NMR fingerprints were used as the guiding principle for the isolation of minor compounds related to the l-type amino acid transporter inhibitors venulosides A (1) and B (2). Two new monoterpene glycosides, namely, venulosides C (3) and D (4), were isolated from a Queensland collection of the plant Pittosporum venulosum. Compounds 3 and 4 were found to inhibit l-leucine transport in LNCaP cells with IC50 values of 11.47 and 39.73 μM, respectively. The venulosides are the first reported natural product inhibitors of leucine transport in prostate cancer cells, and the isolation of the minor compounds provides some early SAR information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / chemistry*
  • Amino Acids / metabolism*
  • Biological Transport
  • Glycosides / chemistry*
  • Glycosides / isolation & purification*
  • Glycosides / pharmacology*
  • Humans
  • Large Neutral Amino Acid-Transporter 1
  • Leucine / metabolism*
  • Male
  • Molecular Structure
  • Monoterpenes / chemistry*
  • Monoterpenes / isolation & purification*
  • Monoterpenes / pharmacology*
  • Nuclear Magnetic Resonance, Biomolecular
  • Rosales / chemistry*
  • Structure-Activity Relationship

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • ESK242
  • ESK246
  • Glycosides
  • Large Neutral Amino Acid-Transporter 1
  • Monoterpenes
  • venuloside C
  • Leucine