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The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of the above lactones to stabilize mast cells. The comparative study with ketotifen and sodium chromoglycate, well known mast cell stabilizers, showed the following order of potency dehydroleucodine=xanthatin>3-benzyloxymethyl-5H-furan-2-one> or =ketotifen/sodium chromoglycate to inhibit mast cell serotonin release induced by compound 48/80. The present study provides the first strong evidence in favour of the hypothesis that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit compound 48/80-induced serotonin release from peritoneal mast cells, acting thus as mast cell stabilizers. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response.

The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58–96% at a dose from 12.5 to 100 mg/kg. These results appear to confirm that the presence of a non-hindered α,β-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.

Seven acetophenone derivatives were isolated from the aerial parts of Ophryosporus axilliflorus (Griseb.) Hieron. These compounds were subjected to the carrageenan-induced mouse paw edema test where tremetone (7) showed extremely anti-inflammatory activity. Furthermore, the non-benzofuran acetophenones 5 and 6, showed a significant response.

Growth-inhibitory activities of selected natural benzofurans (4-9), trans-cinnamic acid derivatives (10-13), chromene compounds (14 and 16), and some semisynthetic derivatives were determined in last instar larvae of Tenebrio molitor via topical administration in Me2CO. The most inhibitory of the tested compounds were 3-gamma, gamma-dimethylallyl-p-coumaric acid (10) and the benzofuran derivative 12-(p-cumaroyloxy)-tremetone (5), the former compound acting on the pupae and the latter on the last instar larvae. Several developmental deficiencies were observed, and some structure-activity relationships are discussed.