Synthesis of inositol 2-phosphate-quercetin conjugates

Carbohydr Res. 1996 Oct 4:292:83-90. doi: 10.1016/s0008-6215(96)91029-0.

Abstract

The antiproliferative flavonoid, quercetin, is limited in its pharmacological utility by its low water solubility. In this paper, we describe the synthesis of two quercetin analogues prepared by linking the hydroxyl group at the 3- or 5-position of the flavonoid to the 1-hydroxyl group of myo-inositol-2-phosphate via a succinate diester linkage. The resulting conjugates were found to have dramatically enhanced water solubility relative to quercetin; the 5-linked quercetin analogue 2 had a water solubility of > 300 mg/mL at 20 degrees C. Comparison of the in vitro cytotoxicity and antiproliferative activity of conjugate 2 with those of quercetin toward cultured human colon adenocarcinoma (SW480) and human glioblastoma (U87MG) cells indicated that this modification of quercetin does not significantly diminish its activity in these assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Humans
  • Inositol Phosphates / chemical synthesis*
  • Inositol Phosphates / chemistry*
  • Inositol Phosphates / pharmacology
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Quercetin / analogs & derivatives*
  • Quercetin / chemical synthesis
  • Quercetin / chemistry
  • Quercetin / pharmacology
  • Solubility
  • Succinates / chemistry
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Inositol Phosphates
  • Succinates
  • inositol 2-monophosphate
  • Quercetin