GLAUCINE ANALOGS AS INHIBITORS OF MOUSE SPLENOCYTE ACTIVITY

The inhibitory effect of 15 semi-synthetic analogues of glaucine (1) o n the lipopolysaccharide (LPS)-induced and the concanavalin A (Con A)- induced proliferation of mouse splenocytes was compared in vitro. Isob oldine (3), bracteoline (4) and dehydroglaucine (9) showed a significa ntly higher potency to suppress LPS-induced proliferation than 1, whil e 7-hydroxy-4-methylglaucine (8), 7-formyldehydroglaucine (11), 7-acet yldehydroglaucine (13), 7-benzoyldehydroglaucine (14), oxoglaucine (15 ) and glaucine-quinol (16) were less inhibitory. Compounds 3, 4, boldi ne (5), 15 and 16 surpassed significantly the inhibition expressed by 1. on Con A-induced proliferative response. The effect was equal to th e inhibition determined for mitomycin C (Mit C) with both mitogens. In contrast to all others analogues, thaliporphine (2) stimulated spleno cyte proliferation in both assays. Antibody response against sheep red blood cells (SRBC) was lowered most strongly by cataline (6), 7-methy ldehydroglaucine (10) and 16.