IJMS, Vol. 18, Pages 2332: Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents

IJMS, Vol. 18, Pages 2332: Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents

International Journal of Molecular Sciences doi: 10.3390/ijms18112332

Authors: Angela Corvino Roberta Rosa Giuseppina Incisivo Ferdinando Fiorino Francesco Frecentese Elisa Magli Elisa Perissutti Irene Saccone Vincenzo Santagada Giuseppe Cirino Maria Riemma Piero Temussi Paola Ciciola Roberto Bianco Giuseppe Caliendo Fiorentina Roviezzo Beatrice Severino

Two series of N-(aryl)-1-(hydroxyalkyl)pyrrolidine-2-carboxamides (2a–2g and 3a–3g) and 1,4-disubstituted 1,2,3-triazoles (5a–5h and 8a–8h) were synthesized. All the compounds, containing a lipophilic tail and a polar headgroup, were evaluated as sphingosine kinase (SphK) inhibitors by assessing their ability to interfere with the acetylcholine (Ach) induced relaxation of aortic rings pre-contracted with phenylephrine. Moreover, their antiproliferative activity was tested on several cell lines expressing both SphK1 and SphK2. Compounds 5h and 8f, identified as the most efficient antiproliferative agents, showed a different selectivity profile, with 8f being selective for SphK1.

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