Biological evaluation of 3'-O-alkylated analogs of salacinol, the role of hydrophobic alkyl group at 3' position in the side chain on the α-glucosidase inhibitory activity

Bioorg Med Chem Lett. 2011 May 15;21(10):3159-62. doi: 10.1016/j.bmcl.2011.02.109. Epub 2011 Mar 29.

Abstract

Four analogs with 3'-O-alkyl groups (9a: CH(3), 9b: C(2)H(5), 9c: C(13)H(27) or 9d: CH(2)Ph) instead of the 3'-O-sulfate anion in salacinol (1), a naturally occurring potent α-glucosidase inhibitor, were synthesized by the coupling reaction of 1,4-dideoxy-1,4-epithio-d-arabinitols (18a and 18b) with appropriate epoxides (10a-10d). These analogs showed equal or considerably higher inhibitory activity against rat small intestinal α-glucosidases than the original sulfate (1), and one of them (9d) was found more potent than currently used α-glucosidase inhibitors as antidiabetics. Thus, introduction of a hydrophobic moiety at the C3' position of this new class of inhibitor was found beneficial for onset of stronger inhibition against these enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation / drug effects*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolase Inhibitors*
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Sugar Alcohols / chemistry*
  • Sugar Alcohols / pharmacology*
  • Sulfates / chemistry*
  • Sulfates / pharmacology*

Substances

  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Sugar Alcohols
  • Sulfates
  • salacinol