Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents
AbstractTwo 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. View Full-Text
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Corvino, A.; Rosa, R.; Incisivo, G.M.; Fiorino, F.; Frecentese, F.; Magli, E.; Perissutti, E.; Saccone, I.; Santagada, V.; Cirino, G.; Riemma, M.A.; Temussi, P.A.; Ciciola, P.; Bianco, R.; Caliendo, G.; Roviezzo, F.; Severino, B. Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents. Int. J. Mol. Sci. 2017, 18, 2332.
Corvino A, Rosa R, Incisivo GM, Fiorino F, Frecentese F, Magli E, Perissutti E, Saccone I, Santagada V, Cirino G, Riemma MA, Temussi PA, Ciciola P, Bianco R, Caliendo G, Roviezzo F, Severino B. Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents. International Journal of Molecular Sciences. 2017; 18(11):2332.Chicago/Turabian Style
Corvino, Angela; Rosa, Roberta; Incisivo, Giuseppina M.; Fiorino, Ferdinando; Frecentese, Francesco; Magli, Elisa; Perissutti, Elisa; Saccone, Irene; Santagada, Vincenzo; Cirino, Giuseppe; Riemma, Maria A.; Temussi, Piero A.; Ciciola, Paola; Bianco, Roberto; Caliendo, Giuseppe; Roviezzo, Fiorentina; Severino, Beatrice. 2017. "Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents." Int. J. Mol. Sci. 18, no. 11: 2332.
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