Suramin analogs inhibit human angiogenesis in vitro.
BACKGROUND
Suramin is a polysulfonated naphthylurea that inhibits tumor cell proliferation and angiogenesis, but the widespread use of this drug has been limited by significant neurologic toxicity. A series of suramin analogs that may exhibit less toxicity in vivo have been synthesized. We hypothesized that these novel analogs would have antiangiogenic properties equal to or greater than those of suramin when evaluated in an in vitro human placental vein angiogenesis model.


METHODS
Human placental veins (n = 72 per group) were cultured in a 0.3% fibrin clot for a period of 14 days. Three suramin analogs (NF 145, NF 248, NF 293) and suramin were tested at 56 and 560 microM concentrations to determine 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 and compared with initiation in a control group (n = 141).


RESULTS
The three suramin analogs inhibited angiogenesis in a dose-dependent fashion, with all compounds exhibiting near-complete inhibition of angiogenesis at 560 microM. The effects of these analogs were equal to or greater than those of suramin.


CONCLUSIONS
Suramin analogs with structural alterations inhibit human angiogenesis at concentrations equivalent to those seen in vivo. These analogs may be more effective antiangiogenic agents than suramin and may have less potential for toxicity.
Meyers
M O
MO
Department of Surgery, Louisiana State University Medical Center, New Orleans, Louisiana 70065, USA.
Gagliardi
A R
AR
Flattmann
G J
GJ
Su
J L
JL
Wang
Y Z
YZ
Woltering
E A
EA
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010920:Placenta / Q000098:blood supply / Q000166:cytology; D011247:Pregnancy; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine; D014680:Veins / Q000187:drug effects
D013498:Suramin