title: Synthesis of quaternary amine ether lipids and evaluation of neoplastic cell growth inhibitory properties.
abstract: Novel quaternary amine ether lipids have been synthesized and tested for inhibition of neoplastic cell proliferation with the HL-60 promyelocytic leukemia cell line. These compounds contain a positively charged quaternary amine functional group attached either directly to the glycerol backbone or at the end of an alkoxy chain. The biological testing has identified several analogues with activity equivalent to or greater than that exhibited by the reference compound in this assay, ET-18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine). Among the most active analogues are compounds 11, [N,N,N-triethyl-3-(hexadecyloxy)-2-ethoxy-1-propylammonium bromide] and 22 [N-[4-[3-(hexadecyloxy)-2-ethoxypropoxy]-1-butyl]pyridinium bromide], which are approximately 3 times as active as the reference standard.
authors.affiliation: University of North Carolina, School of Pharmacy, Division of Medicinal Chemistry and Natural Products, Chapel Hill 27599.
authors.forename: S L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.forename: K L
authors.initials: KL
authors.lastname: Meyer
authors.forename: C J
authors.initials: CJ
authors.lastname: Marasco
authors.forename: C
authors.initials: C
authors.lastname: Piantadosi
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: P L
authors.initials: PL
authors.lastname: Godwin
authors.forename: E J
authors.initials: EJ
authors.lastname: Modest
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D008055:Lipids / Q000138:chemical synthesis / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D004987:Ethers; D008055:Lipids; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D011493:Protein Kinase C