Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter

Bioorg Med Chem. 2010 Mar 15;18(6):2152-2158. doi: 10.1016/j.bmc.2010.01.077. Epub 2010 Feb 6.

Abstract

Three new picraline-type alkaloids, alstiphyllanines E-G (1-3) and a new ajmaline-type alkaloid, alstiphyllanine H (4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids (5-20). Structures and stereochemistry of 1-4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F (1 and 2) showed moderate Na(+)-glucose cotransporter (SGLT1 and SGLT2) inhibitory activity. A series of a hydroxy substituted derivatives 21-28 at C-17 of the picraline-type alkaloids have been derived as having potent SGLT inhibitory activity. 10-Methoxy-N(1)-methylburnamine-17-O-veratrate (6) exhibited potent inhibitory activity, suggesting that the presence of an ester side chain at C-17 may be important to show SGLT inhibitory activity. Structure activity relationship of alstiphyllanines on inhibitory activity of SGLT was discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alstonia / chemistry*
  • Animals
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / pharmacology*
  • Molecular Conformation
  • Plant Leaves / chemistry*
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors*
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Indole Alkaloids
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2 Inhibitors
  • alstiphyllanine E
  • alstiphyllanine H