New xanthone derivatives as potent anti-inflammatory agents.

A series of novel xanthone derivatives were synthesized as potential anti-inflammatory compounds. The compounds were examined for anti-inflammatory and analgesic properties. Aspirin and ketoprofen were used as reference compounds.

METHODS

Acute inflammation was induced by subplantar injection of 0.1 ml of 1% carrageenan solution to the right rat paw, 1 hour after oral administration of the investigated compound. The development of paw edema was measured plethysmographically. Pain threshold in the hind paw of rat affected by inflammation was measured using an analgesimeter 4 hours after oral administration of the compounds. Mean pain thresholds were calculated for treated and control groups and the percent change from control was determined. Thus we observed irritation of gastric mucosa after use of compounds, which showed significant anti-inflammatory activity. The mucosa of the glandular part of the stomach was inspected using a binocular microscope.

RESULTS

The preliminary investigation of the anti-inflammatory activity of the novel xanthone derivatives showed uneven anti-inflammatory and analgesic activity. The highest anti-inflammatory and analgesic activity was provided by compound MH-44. The compounds MH-41, MH-43 and MH-48 potentiated the carrageenan edema and lowered the threshold pain in comparison with control. Side effects of the active compound were examined on gastric mucosa and stomach and none of the active compounds showed significant side effects compared with nonsteroidal anti-inflammatory drugs.

CONCLUSIONS

None of the active compounds showed significant side effects compared with nonsteroidal anti-inflammatory drugs.