Functionalized pyrrolidine inhibitors of human alpha- mannosidases II in cancer: optimizing the fit to the active site

Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi α- mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of α-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.


Published in:
Bioorganic and Medicinal Chemistry, 16, 7337-7346
Year:
2008
Keywords:
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 Record created 2008-06-05, last modified 2018-09-13


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