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

The antitumor agent, paclitaxel (Taxol(R)), mimics the actions of lipopolysaccharide (LPS) on murine macrophages (M phi), Various synthetic analogs of paclitaxel mere examined for their potencies to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by murine peritoneal M phi, 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 sere found to be critically important sites to activate murine M phi. 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. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.