Functionalized pyrrolidine inhibitors of human type II alpha-mannosidases as anti-cancer agents: optimizing the fit to the active site
Fiaux, H., Kuntz, D.A., Hoffman, D., Janzer, R.C., Gerber-Lemaire, S., Rose, D.R., Juillerat-Jeanneret, L.(2008) Bioorg Med Chem 16: 7337-7346
- PubMed: 18599296 
- DOI: https://doi.org/10.1016/j.bmc.2008.06.021
- Primary Citation of Related Structures:  
3DDF, 3DDG - PubMed Abstract: 
Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi alpha-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of alpha-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.
Organizational Affiliation: 
Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.