Angiostatic effects of suramin analogs in vitro

Suramin analogs are polyanionic naphthylureas structurally related to suram in, an antitumor agent with a narrow therapeutic window. The angiostatic ac tivities of suramin and 16 suramin analogs were investigated using an easil y quantifiable in vitro angiogenesis system. in addition, the antiprolifera tive activities of the analogs were studied in four different human tumor c ell lines and in porcine aortic endothelial cells. The suramin analogs enco mpassed two main structural variations, i.e. their molecular size, and the number and substitution pattern of the sulfonate groups. Some suramin analo gs with a reduced number of sulfonate groups (NF062, NF289 and NF326) showe d significant dose-dependent angiostatic and also antiproliferative activit ies. The disulfonate NF062 was superior to suramin in inhibiting HT29 and T 47D tumor cells while demonstrating a similar angiostatic potential as sura min. Therefore, the sulfonate groups in the para position of the amino grou ps of the naphthyl residues of suramin seem to be of special importance. Th e very small disulfonates (NF108, NF109, NF499, NF500 and NF241) and the as ymmetric compound NF520, one half of the suramin molecule, are inactive. Th erefore, a minimal molecule size seems to be essential for the biological a ctivity. Suramin is a rather rigid molecule. The highly flexible analogs (N F527, NF528 and NF529) are inactive. This indicates that the molecular rigi dity is important for the biological activity. [(C) 2000 Lippincott William s & Wilkins.].