SYNTHESIS OF INOSITOL 2-PHOSPHATE-QUERCETIN CONJUGATES

The antiproliferative flavonoid, quercetin, is limited in its pharmaco logical utility by its low water solubility. In this paper, we describ e the synthesis of two quercetin analogues prepared by linking the hyd roxyl 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, Th e resulting conjugates were found to have dramatically enhanced water solubility relative to quercetin; the 5-linked quercetin analogue 2 ha d a water solubility of > 300 mg/mL at 20 degrees C, Comparison of the in vitro cytotoxicity and antiproliferative activity of conjugate 2 w ith those of quercetin toward cultured human colon adenocarcinoma (SW4 80) and human glioblastoma (U87MG) cells indicated that this modificat ion of quercetin does not significantly diminish its activity in these assays. (C) 1996 Elsevier Science Ltd.