In vitro evaluation of phosphocholine and quaternary ammonium containing lipids as novel anti-HIV agents

A series of synthetic lipids containing a two- or three-carbon backbone substituted with a thio, oxy, or amidoalkyl functionality and either a phosphocholine or quaternary ammonium moiety was evaluated as potential anti-HIV-1 agents. Several analogues were identified as possessing activity with the...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of medicinal chemistry Vol. 34; no. 4; pp. 1377 - 1383
Main Authors:	Meyer, Karen L, Marasco, Canino J, Morris-Natschke, Susan L, Ishaq, Khalid S, Piantadosi, Claude, Kucera, Louis S
Format:	Journal Article
Language:	English
Published:	Washington, DC American Chemical Society 01-04-1991
Subjects:	AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - chemical synthesis Biological and medical sciences Cell Division - drug effects Cell Line DNA Replication - drug effects HIV-1 - drug effects HIV-1 - physiology Humans Indicators and Reagents Magnetic Resonance Spectroscopy Medical sciences Molecular Structure Pharmacology. Drug treatments Phospholipid Ethers - chemical synthesis Phospholipid Ethers - chemistry Phospholipid Ethers - pharmacology Quaternary Ammonium Compounds - chemical synthesis Quaternary Ammonium Compounds - chemistry Quaternary Ammonium Compounds - pharmacology Structure-Activity Relationship Viral Plaque Assay Virus Replication - drug effects Zidovudine - pharmacology Ether Retroviridae Phospholipid Lipids Complex lipid In vitro Virus Quaternary ammonium compound Structure activity relation Analog Lentivirinae Antiviral Human immunodeficiency virus
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	A series of synthetic lipids containing a two- or three-carbon backbone substituted with a thio, oxy, or amidoalkyl functionality and either a phosphocholine or quaternary ammonium moiety was evaluated as potential anti-HIV-1 agents. Several analogues were identified as possessing activity with the most promising compound being rac-3-octadecanamido-2-ethoxypropylphosphocholine (8). Compound 8 exhibited an IC50 for the inhibition of plaque formation of 0.16 microM which was 84-fold lower than the IC50 value determined for CEM-SS cell growth inhibition. Initial mechanistic studies have indicated that these compounds, unlike AZT, are not reverse transcriptase (RT) inhibitors, but instead appear to inhibit a late step in HIV replication involving virus assembly and infectious virus production. Since these lipids are acting via a different mechanism, they represent an alternative approach to the chemotherapeutic treatment of AIDS as well as candidates for combination therapy with AZT.
Bibliography:	ark:/67375/TPS-CR8C60KN-3 istex:04E7C68C5EE73D42E022A8D5AB3E593C7C0EF9EC ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm00108a021