Next Article in Journal
Simultaneous Determination and Investigation of Nine Fungicides in Fruits Using Diethylenetriamine-Functional Magnetic Core-Shell Polymer Modified Graphene Oxide as an Efficient Adsorbent Coupled to UPLC-HRMS
Next Article in Special Issue
Sphingosine 1-Phosphate (S1P) Signaling in Glioblastoma Multiforme—A Systematic Review
Previous Article in Journal
UVA, UVB Light, and Methyl Jasmonate, Alone or Combined, Redirect the Biosynthesis of Glucosinolates, Phenolics, Carotenoids, and Chlorophylls in Broccoli Sprouts
Previous Article in Special Issue
Sphingosine Kinase 1 and Sphingosine-1-Phosphate Signaling in Colorectal Cancer
Open AccessArticle

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

Graphical abstract

MDPI and ACS Style

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop