Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1378689 | Bioorganic & Medicinal Chemistry Letters | 2006 | 6 Pages |
Abstract
Prompted by the therapeutic potential of the neuroimmunophilin FK506-binding protein (FKBP) ligand, GPI-1046, in the treatment of nerve injuries and neurodegenerative diseases, a novel series of non-cyclic derivatives of GPI-1046 were designed and synthesized. Computer modeling analysis revealed that these relatively linear derivatives could energy-favorably bind to FKBP12 with an analogous binding mode to GPI-1046. The neurotrophic activity of the target compounds was assessed in chick dorsal root ganglion (DRG) cultures. As a result, 6 out of 11 test compounds at either or both concentrations of 1Â pM and 100Â pM significantly promoted neurite outgrowth in DRGs in the presence of 0.15Â ng/ml nerve growth factor (NGF). Compound 5c at 100Â pM exhibited the greatest neurotrophic effect in promoting both the number and length of neurite processes. However, in the absence of exogenously added NGF, all test compounds, including GPI-1046, failed to afford any positive effect on DRGs. This study suggests the intriguing potential of these compounds for further investigation.
Keywords
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Liqin Zhao, Hongying Liu, Lili Wang, Song Li,