Pope L E, Marcelletti J F, Katz L R, Katz D H
LIDAK Pharmaceuticals, La Jolla, CA 92037, USA.
J Lipid Res. 1996 Oct;37(10):2167-78.
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.
22碳脂肪醇正二十二醇对包括单纯疱疹病毒1型和2型在内的几种包膜病毒具有体外抗病毒活性，其作用机制是干扰病毒正常进入靶细胞。我们之前报道过哺乳动物细胞会摄取大量放射性标记的正二十二醇。在此，我们报告细胞会广泛代谢内化的脂肪醇。这一点可通过高达60%的细胞相关放射性标记掺入与磷脂酰胆碱和磷脂酰乙醇胺共纯化的磷脂中得到证明。化学（红铝）还原分析表明，相当一部分正二十二醇被氧化为正二十二酸，然后作为酰基掺入极性脂质中。然而，可测量的放射性标记量对红铝还原具有抗性，这与正二十二醇掺入醚脂一致。正二十二醇的代谢转化速率和程度因细胞类型和用于悬浮该化合物的表面活性剂而异。此外，正二十二醇的抗单纯疱疹病毒活性与观察到的代谢量呈定量比例关系。这些发现表明正二十二醇的抗单纯疱疹病毒活性涉及药物的细胞摄取和代谢。
