Structural significance of the acyl group at the C‐10 position and the A ring of the taxane core of paclitaxel for inducing nitric oxide and tumor necrosis factor production by murine macrophages

FEBS Letters

Fuero-Oderda, Cecilia²  Nakano, Masayasu¹  Ojima, Iwao²  Hashimoto, Masahito³  Kirikae, Teruo³  Lin, Songnian²  Kirikae, Fumiko³ 

[1] Department of Microbiology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken 329-0498, Japan;Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA;Department of Infectious Diseases and Tropical Medicine, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan

关键词: Lipopolysaccharide;    Paclitaxel;    Macrophage;    Lipopolysaccharide low responder;    Nitric oxide;    Tumor necrosis factor;    IFNγ;    interferon γ;    iNOS;    inducible nitric oxide synthase;    LPS;    lipopolysaccharide;    Mφ;    macrophages;    NO;    nitric oxide;    TNF;    tumor necrosis factor;   

DOI  :  10.1016/S0014-5793(00)01858-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The antitumor agent, paclitaxel (Taxol^®), mimics the actions of lipopolysaccharide (LPS) on murine macrophages (Mφ). Various synthetic analogs of paclitaxel were examined for their potencies to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by murine peritoneal Mφ, 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 Mφ. 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.

【 授权许可】

Unknown