MEDI 372 |
| Schistosomiasis is an endemic parasitic disease found in 74 countries. It has been estimated that at least 200 million people are currently infected, with over 1.7 million DALYs per year. The parasite Schistosoma mansoni lacks the de novo pathway and depends on the purine salvage pathway for its purine supply. Purine nucleoside phosphorylase (PNP) is a key enzyme of the purine salvage pathway and has been recognized as an promising target for drug design. In the present work, we describe the structure-activity relationships for a series of S. mansoni PNP inhibitors. Values of IC50 were collected employing a standard coupled assay. Molecular modeling studies were carried out using the docking programs GOLD e FlexX and the results revealed essential protein–ligand interactions in the PNP active site. The understanding of these intermolecular interactions is essential for the design of new inhibitors of S. mansoni PNP having improved potency and selectivity. |
|
General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Division of Medicinal Chemistry |