Suramin, a polyanionic naphthylurea, represents a novel class of antineoplastic drugs with a variety of activities against tumor cell proliferation. However, its clinical use is hampered by serious toxicity. To gain more insight into structure-activity relationships of suramin, we investigated the antiproliferative action of suramin and 19 suramin analogues in vitro using 5 different human cell lines (HT29, MCF7, SW13, PC3, and T47D). In addition, for seven analogues the angiostatic potential 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 (IC50 = 43–390 µm), indicating that besides the polyanionic feature, other structural elements are important (e.g., stiffness of the bridge between 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 action. Hydrocortisone increased the angiostatic effect of most but not all of the screened suramin analogues. These findings may guide the use of suramin analogues for improved antitumor therapy in vivo.

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Supported by Deutsche Forschungsgemeinschaft AI 203/4.1. This work is part of the doctoral thesis of A. F.

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