Anti-inflammatory alkaloids from the stems of Picrasma quassioides BENNET.

During further chemical and biological investigations of Picrasma quassioides BENNET, four new bis-ß-carboline alkaloids, quassidines E-H (1-4), and three new ß-carboline alkaloids, canthin-16-one-14-butyric acid (5), 3-(1,1-dimethoxylmethyl)-ß-carboline (6), and 6,12-dimethoxy-3-formyl-ß-carboline (7), were isolated from its anti-inflammatory CHCl(3)-soluble fraction. Structures of new compounds were elucidated and characterized by MS and NMR analysis. A plausible biogenetic pathway for quassidine E (1), the first bis-ß-carboline alkaloid in which a canthin-6-one moiety and a ß-carboline moiety were connected together by a single carbon-carbon bond from the nature, was proposed. Quassidines E-G (1-3) showed potent inhibitory activity on the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), or interleukin 6 (IL-6) in mouse monocyte-macrophage RAW264.7 cells stimulated by lipopolysaccharide (LPS). Analysis of anti-inflammatory activity of all ß-carboline and bis-ß-carboline alkaloids from P. quassioides showed that the carbonyl groups or double carbon-carbon bonds at C-14 for ß-carbolines and C-14' for bis-ß-carbolines were bioactive groups for their in vitro anti-inflammatory activity. Structure-activity relationship of these compounds on inhibitory activity of the three inflammatory cytokines was discussed.