title: Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C.
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.
authors.affiliation: University of North Carolina, School of Pharmacy, Division of Medicinal Chemistry and Natural Products, Chapel Hill 27599.
authors.forename: C J
authors.initials: CJ
authors.lastname: Marasco
authors.forename: C
authors.initials: C
authors.lastname: Piantadosi
authors.forename: K L
authors.initials: KL
authors.lastname: Meyer
authors.forename: S
authors.initials: S
authors.lastname: Morris-Natschke
authors.forename: K S
authors.initials: KS
authors.lastname: Ishaq
authors.forename: G W
authors.initials: GW
authors.lastname: Small
authors.forename: L W
authors.initials: LW
authors.lastname: Daniel
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D010718:Phosphatidylserines / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004075:Diglycerides; D010718:Phosphatidylserines; D010742:Phospholipid Ethers; C026659:edelfosine; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C