Abstract
The antitumor agent, paclitaxel (Taxol), mimics the actions of lipopolysaccharide (LPS) on murine macrophages (Mphi). Various synthetic analogs of paclitaxel were examined for their potencies to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by murine peritoneal Mphi, and by human peripheral blood cells. The benzoyl group at C-2, the hydroxy group at C-7 and the acetyl group at C-10 were found to be critically important sites to activate murine Mphi. Nor-seco-taxoid analogs lacking the A ring of the taxane core of paclitaxel were inactive, but inhibit paclitaxel- or LPS-induced NO production. All the compounds tested did not induce TNF production by human blood cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acylation
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Animals
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Bridged-Ring Compounds / chemistry*
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Cell Division / drug effects
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Cells, Cultured
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Enzyme Induction / drug effects
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Humans
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Inhibitory Concentration 50
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / metabolism
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / drug effects*
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Macrophages, Peritoneal / metabolism
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Mice
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Mice, Inbred C3H
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase Type II
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Paclitaxel / analogs & derivatives*
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Paclitaxel / antagonists & inhibitors
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Paclitaxel / chemistry
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Paclitaxel / pharmacology*
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Taxoids*
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Tumor Necrosis Factor-alpha / biosynthesis*
Substances
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Bridged-Ring Compounds
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Lipopolysaccharides
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Taxoids
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Tumor Necrosis Factor-alpha
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taxane
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Nitric Oxide
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Paclitaxel