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Diaz L.,Spanish National Research Council Consejo Superior Of Investigaciones Cientificas Csic | Casas J.,Spanish National Research Council Consejo Superior Of Investigaciones Cientificas Csic | Bujons J.,CSIC - Institute of Advanced Chemistry of Catalonia | Llebaria A.,Spanish National Research Council Consejo Superior Of Investigaciones Cientificas Csic | And 2 more authors.
Journal of Medicinal Chemistry | Year: 2011

A library of aminocyclitols derived from CuAAC reaction between N-propargylaminocyclitol 4 and a series of azides [1′25] is described and tested against GCase. Azides have been chosen from a large collection of potential candidates that has been filtered according to physical and reactivity constraints. A synthetic methodology has been optimized in order to avoid the use of protecting groups on the aminocyclitol scaffold. Because the reaction can be carried out in an aqueous system, the resulting library members can be screened in situ with minimal manipulation. From the preliminary GCase inhibition data, the most potent library members have been individually resynthesized for further biological screening and complete characterization. Some of the library members have shown biochemical data (IC50, K i, and stabilization ratio) similar or superior to those reported for NNDNJ. Docking studies have been used to postulate ligand-enzyme interactions to account for the experimental results. © 2011 American Chemical Society. Source


Delgado A.,Spanish National Research Council Consejo Superior Of Investigaciones Cientificas Csic | Delgado A.,CSIC - Institute of Advanced Chemistry of Catalonia | Delgado A.,University of Barcelona | Fabrias G.,Spanish National Research Council Consejo Superior Of Investigaciones Cientificas Csic | And 5 more authors.
Advances in Cancer Research | Year: 2013

Modulation of sphingolipid metabolism is a promising strategy for cancer therapy that has already opened innovative approaches for the development of pharmacological tools and rationally designed new drugs. On the other hand, natural products represent a classical and well-established source of chemical diversity that has guided medicinal chemists on the development of new chemical entities with potential therapeutic use. Based on these premises, the aim of this chapter is to provide the reader with a general overview of some of the most representative families of sphingolipid-related natural products that have been described in the recent literature as lead compounds for the design of new modulators of sphingolipid metabolism. Special emphasis is placed on the structural aspects of natural sphingoids and synthetic analogs that have found application as anticancer agents. In addition, their cellular targets and/or their mode of action are also considered. © 2013 Elsevier Inc. Source

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