Premium
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
Author(s) -
Kirikae Teruo,
Ojima Iwao,
Fuero-Oderda Cecilia,
Lin Songnian,
Kirikae Fumiko,
Hashimoto Masahito,
Nakano Masayasu
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01858-5
Subject(s) - taxane , paclitaxel , nitric oxide , tumor necrosis factor alpha , lipopolysaccharide , chemistry , pharmacology , docetaxel , apoptosis , biochemistry , medicine , chemotherapy , immunology , cancer , breast cancer , organic chemistry
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.