Document Report Card

ID: ALA1124731

Journal: J Med Chem

Title: Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C.

Authors: Marasco CJ, Piantadosi C, Meyer KL, Morris-Natschke S, Ishaq KS, Small GW, Daniel LW.

Abstract: Alkylglycerols such as rac-1-O-octadecyl-2-O-methylglycerophosphochocholine (Et-18-OMe) have shown an inhibitory effect on the metastasis and growth of various cancer cell lines. Alkyl phospholipids have been shown to accumulate at the surface in several cell lines, the selectivity of which is still not clearly understood. A consequence of this action may lead to the inhibition of cell membrane related protein kinase C (PKC). The goal of this research was to develop ether lipid inhibitors of PKC to augment antineoplastic activity. This led to the synthesis and in vitro testing of a series of novel quaternary ammonium derivatives of alkylglycerols. The biological testing of these analogues on PKC stimulated with rac-1-O-oleoyl-2-O-acetylglycerol showed several analogues with inhibition comparable to that of Et-18-OMe.

CiteXplore: 2308148

DOI: 10.1021/jm00165a016