Synthesis and anti-inflammatory effects of xanthone derivatives.

Eighteen synthetic xanthone derivatives were tested for their inhibitory effects on the activation of mast cells and neutrophils. 1,3- and 3,5-Dihydroxyxanthone showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. 1,6-Dihydroxyxanthone and 1,3,8-trihydroxyxanthone showed strong inhibitory effects on the release of beta-glucuronidase, and beta-glucuronidase and lysozyme, respectively, from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). 1,3- and 1,6-Dihydroxyxanthone, 1,3,7-trihydroxyxanthone, and 1,3,5,6-, 2,3,6,7-, and 3,4,5,6-tetrahydroxyxanthone showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP. 1,6- and 3,5-Dihydroxyxanthone showed remarkable inhibitory effects on hind-paw oedema induced by polymyxin B in normal as well as in adrenalectomized mice. These data indicated that the anti-inflammatory effect of these compounds is mediated through the suppression of chemical mediators released from mast cell and neutrophil degranulation.