Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88)

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. doi:10.1021/jm050618p


Author Karoli, Tomislav
Liu, Ligong
Fairweather, Jon K.
Hammond, Edward
Li, Cai Ping
Cochran, Siska
Bergefall, Kicki
Trybala, Edward
Addison, Russell S.
Ferro, Vito
Title Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88)
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
Publication date 2005-01-01
Year available 2005
Sub-type Article (original research)
DOI 10.1021/jm050618p
Open Access Status Not yet assessed
Volume 48
Issue 26
Start page 8229
End page 8236
Total pages 8
Editor P. S. Portoghese
L. H. Hurley
Place of publication Washington, U.S.A.
Publisher American Chemical Society
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730108 Cancer and related disorders
030503 Organic Chemical Synthesis
030401 Biologically Active Molecules
Abstract 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.
Keyword Chemistry, Medicinal
Oligosaccharide Phosphate Fraction
Nrrl Y-2448 Phosphomannan
Herpes-simplex-virus
Heparan-sulfate
In-vitro
Anticoagulant
Growth
Cancer
Model
Q-Index Code C1
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 57 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 57 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 17:20:59 EST