Glucal-conjugated sterols as novel vascular leakage blocker: structure-activity relationship focusing on the C17-side chain

Eur J Med Chem. 2014 Mar 21:75:184-94. doi: 10.1016/j.ejmech.2014.01.027. Epub 2014 Jan 25.

Abstract

A series of glucal-conjugated sterols as novel vascular leakage blocker were identified through design, synthesis and biologically evaluation. In addition, the structure-activity relationship (SAR) of the glucal-conjugated sterols focusing on the C17-side chain was also established. The sterol analogs linked with the rigid C17-side chain side chains exhibited potent cell survival activities. In particular, analog 21l, which possesses a cyclopentyl oxime moiety, was shown to have excellent pharmacological effects on retinal vascular leakage in a diabetic mouse model.

Keywords: Anti-apoptotic agents; Diabetic retinopathy; Ginsenoside Rk1; Oxime; Pregnenolone; Tight junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Calcium Gluconate / chemical synthesis
  • Calcium Gluconate / chemistry*
  • Calcium Gluconate / pharmacology*
  • Cell Line
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / pathology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / pathology
  • Human Umbilical Vein Endothelial Cells
  • Mice
  • Mice, Inbred C57BL
  • Oximes / chemical synthesis
  • Oximes / chemistry
  • Oximes / pharmacology
  • Permeability / drug effects
  • Retina / cytology
  • Retina / drug effects
  • Retina / pathology
  • Sterols / chemical synthesis
  • Sterols / chemistry*
  • Sterols / pharmacology*
  • Structure-Activity Relationship

Substances

  • Oximes
  • Sterols
  • Calcium Gluconate