SYNTHESIS AND BIOLOGICAL EVALUATION OF INOSITOL DERIVATIVES AS INHIBITORS OF PHOSPHOLIPASE-C

The synthesis and biological evaluation of analogues of phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) is described. Inositol derivatives with and without homologation at C(1) and with and without ionic groups (phosphate or sulfate) at C(4) and C(5) were prepared. In all these compounds, palmitate ester groups were introduced in place of the diacylglyceryl group of PI or PIP2. All compounds with ionic groups (sulfates or phosphates) were found to inhibit phospholipase C (PLC) in vitro significantly. In contrast, compounds without ionic groups showed only a slight degree of inhibition. Some of the compounds with ionic groups have also been tested for PLC inhibition in intact cells and were found to be inactive in this assay.