<< Back to Publication List
|2005 ||Karoli, Tomislav, Liu, Ligong, Fairweather, Jon K., Hammond, Edward, Li, Cai Ping, Cochran, Siska, Bergefall, Kicki, Trybala, Edward, Addison, Russell S. and Ferro, Vito (2005) Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88). Journal of Medicinal Chemistry, 48 26: 8229-8236.|
The phosphosulfomannan 1 (PI-88) is a mixture of highly sulfated oligosaccharides that is currently undergoing clinical evaluation in cancer patients. As well as it's anticancer properties, 1 displays a number of other interesting biological activities. A series of analogues of 1 were synthesized with a single carbon (pentasaccharide) backbone to facilitate structural characterization and interpretation of biological results. In a fashion similar to 1, all compounds were able to inhibit heparanase and to bind tightly to the proangiogenic growth factors FGF-1, FGF-2, and VEGF. The compounds also inhibited the infection of cells and cell-to-cell spread of herpes simplex virus (HSV-1). Preliminary pharmacokinetic data indicated that the compounds displayed different pharmacokinetic behavior compared with 1. Of particular note was the n-octyl derivative, which was cleared 3 times less rapidly than 1 and may provide increased systemic exposure.
| Dr Russell Addison, Dr Ligong Liu, Assoc Prof Vito Ferro|
|eSpace Record: |
| || |
|Links: ||Article DOI - full text from publisher|
|Keywords: ||Chemistry, Medicinal, Oligosaccharide Phosphate Fraction, Nrrl Y-2448 Phosphomannan, Herpes-simplex-virus, Heparan-sulfate, In-vitro, Anticoagulant, Growth, Cancer, Model|