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.
Lin
C N
CN
School of Pharmacy, Kaohsiung Medical College, Taiwan, R.O.C.
Chung
M I
MI
Liou
S J
SJ
Lee
T H
TH
Wang
J P
JP
D000315:Adrenalectomy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005966:Glucuronidase / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D011112:Polymyxin B / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D014966:Xanthenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014966:Xanthenes; D013481:Superoxides; D009113:Muramidase; D005966:Glucuronidase; D011112:Polymyxin B