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Journal of Lipid Research, Vol 37, 2167-2178, Copyright © 1996 by Lipid Research, Inc.
LE Pope, JF Marcelletti, LR Katz and DH Katz
The 22-carbon fatty alcohol, n-docosanol, exhibits in vitro antiviral
activity against several lipid-enveloped viruses including herpes simplex
viruses 1 and 2 by a mechanism that interferes with normal viral entry into
target cells. We previously reported that mammalian cells incorporate
significant quantities of radiolabeled n-docosanol. Herein, we report that
cells extensively metabolize the internalized fatty alcohol. This is
evidenced by incorporation of up to 60% of cell- associated radiolabel into
phospholipids that copurify with phosphatidylcholine and
phosphatidylethanolamine. Analysis by chemical (Vitride) reduction suggests
that a significant portion of n-docosanol is oxidized to n-docosanoic acid
and then incorporated as an acyl group on polar lipids. A measurable amount
of radiolabel, however, is resistant to Vitride reduction, consistent with
incorporation of n- docosanol into ether lipids. The rate and extent of
metabolic conversion of n-docosanol vary with the cell type and surfactant
used to suspend the compound. Furthermore, the anti-HSV activity of n-
docosanol is quantitatively proportional to the amount of metabolism
observed. These findings suggest that the anti-HSV activity of n- docosanol
involves cellular uptake and metabolism of the drug.
ARTICLES
Anti-herpes simplex virus activity of n-docosanol correlates with intracellular metabolic conversion of the drug
LIDAK Pharmaceuticals, La Jolla, CA 92037, USA.
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