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Int. J. Mol. Sci. 2017, 18(11), 2332; https://doi.org/10.3390/ijms18112332

Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents

1
Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
2
Department of Clinical Medicine and Surgery, Oncology Division, University of Naples Federico II, 80131 Naples, Italy
3
The Wohl Institute, King’s College London, 5 Cutcombe Rd, London SE5 9RT, UK
*
Author to whom correspondence should be addressed.
Received: 19 October 2017 / Revised: 31 October 2017 / Accepted: 1 November 2017 / Published: 5 November 2017
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

Two series of N-(aryl)-1-(hydroxyalkyl)pyrrolidine-2-carboxamides (2a2g and 3a3g) and 1,4-disubstituted 1,2,3-triazoles (5a5h and 8a8h) 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
Keywords: Sphingosine Kinase 1; Sphingosine Kinase 2; inhibitors; synthesis; antiproliferative activity Sphingosine Kinase 1; Sphingosine Kinase 2; inhibitors; synthesis; antiproliferative activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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