Suramin analogs inhibit human angiogenesis in vitro

Background. Suramin is a polysulfonated naphthylurea that inhibits tumor ce ll proliferation and angiogenesis, but the widespread use of this drug has been limited by significant neurologic toxicity. A series of suramin analog s that may exhibit less toxicity in vivo have been synthesized. We hypothes ized that these novel analogs mould have antiangiogenic properties equal to or greater than those of suramin when evaluated in an in vitro human place ntal vein angiogenesis model. Methods. Human placental veins (n = 72 per group) were cultured in a 0.3% f ibrin clot for a period of 14 days. Three suramin analogs (NF 145, NF 248, NF 293) and suramin were tested at 56 and 560 mu M concentrations to determ ine their effect on the development of an angiogenic response. Experiments were repeated for each analog on veins from three different placentas. The percentage of wells that initiated an angiogenic response was calculated an d compared with initiation in a control group (n = 141). Results. The three suramin analogs inhibited angiogenesis in a dose-depende nt fashion, with all compounds exhibiting near-complete inhibition of angio genesis at 560 mu M. The effects of these analogs were equal to or greater than those of suramin. Conclusion. Suramin analogs with structural alterations inhibit human angio genesis at concentrations equivalent to Obese seen in vivo. These analogs m ay be more effective antiangiogenic agents than suramin and may have less p otential for toxicity. (C) 2000 Academic Press.