ANTIPROLIFERATIVE AND ANGIOSTATIC ACTIVITY OF SURAMIN ANALOGS

Suramin, a polyanionic naphthylurea, represents a novel class of antin eoplastic drugs with a variety of activities against tumor cell prolif eration. However, its clinical use is hampered by serious toxicity. To gain more insight into structure-activity relationships of suramin, w e investigated the antiproliferative action of suramin and 19 suramin analogues in vitro using 5 different human cell Lines (HT29, MCF7, SW1 3, PC3, and T47D). In addition, for seven analogues the angiostatic po tential with and without hydrocortisone was assessed using a modified chorioallantois membrane assay. Only the symmetric compounds exhibited antiproliferative action in vitro; several analogues were more active than suramin (e.g., NF031, NF037, NF326). Suramin analogues with six sulfonic acid groups showed a wide range of activity in HT29 cells (IC 50 = 43-390 mu M), indicating that besides the polyanionic feature, ot her structural elements me important (e.g., stiffness of the bridge be tween the two terminal naphthyl rings). Some of the smaller ureas with only four sulfonic acid groups retained significant antiproliferative activity. Compounds active in cell lines also inhibited angiogenesis in the chorioallantois membrane assay, suggesting a similar mode of ac tion. Hydrocortisone increased the angiostatic effect of most but not all of the screened suramin analogues. These findings may guide the us e of suramin analogues for improved antitumor therapy in vivo.