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• W2040796031 abstract "The antitumor agent paclitaxel (Taxol) mimics the actions of lipopolysaccharide (LPS) on murine macrophages (Mφ). Recently, we have shown that the benzoyl group at the C-3′ position of paclitaxel is the most important site to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by C3H/HeN Mφ (Biochem. Biophys. Res. Commun.210, 678–686, 1996). In the present study, synthetic analogs of paclitaxel with replacement of the C-3′-N position were examined for their potencies to induce NO and TNF production by peritoneal Mφ of LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice, by human blood cells and human Mφ. In this structure-activity relationship study, we found that (i) thep-substitution of the benzoyl group definitely affects the activity to activate C3H/HeN Mφ, (ii) the analogs having a methyl or chloro group at thep-position exhibit stronger activity than that of paclitaxel, (iii) there is good correlation between NO and TNF production by the Mφ in response to compounds, (iv) the compounds tested do not induce either NO or TNF production by C3H/HeJ Mφ or TNF production by human cells, (v) a previous treatment of C3H/HeN Mφ with the inactive compounds can hardly affect either paclitaxel- or LPS-induced TNF production by the Mφ, (vi) paclitaxel and its analogs marginally affect LPS-induced TNF production by human blood cells, and (vii) there is no correlation between the NO/TNF inducibility to C3H/HeN Mφ and growth inhibitory activity against Mφ-like J774.1 and J7.DEF3 cells." @default.
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• W2040796031 date "1998-04-01" @default.
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• W2040796031 title "Structural Significance of the Benzoyl Group at the C-3′-N Position of Paclitaxel for Nitric Oxide and Tumor Necrosis Factor Production by Murine Macrophages" @default.
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• W2040796031 doi "https://doi.org/10.1006/bbrc.1998.8409" @default.
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