Inhibition of leukocyte functions by the alkaloid isaindigotone from Isatis indigotica and some new synthetic derivatives.

The alkaloid isaindigotone (1a) and seven derivatives have been synthesized to study their influence on several leukocyte functions and the generation of inflammatory mediators. Isaindigotone (1a) was found to be a scavenger of superoxide generated either by the hypoxanthine/xanthine oxidase system or stimulated human neutrophils. Isaindigotone (1a) and its acetylated derivative (1b) also inhibited 5-lipoxygenase activity and leukotriene B(4) production in these cells, whereas none of the compounds affected degranulation. In RAW 264.7 macrophages stimulated with lipopolysaccharide, synthetic derivatives exerted higher inhibitory effects on prostaglandin E(2) (PGE(2)) and nitric oxide (NO) g…