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Synthetic Sphingolipids with 1,2-Pyridazine Appendages Improve Antiproliferative Activity in Human Cancer Cell Lines
Sylvestre P J T Bachollet1, Vito Vece1, Alison N McCracken2
1Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, Quebec H3C 3J7, Canada.
Abstract:
A synthetic sphingolipid related to a ring-constrained hydroxymethyl pyrrolidine analog of FTY720 that was known to starve cancer cells to death was chemically modified to include a series of alkoxy-tethered 3,6-substituted 1,2-pyridazines. These derivatives exhibited excellent antiproliferative activity against eight human cancer cell lines from four different cancer types. A 2.5- to 9-fold reduction in IC50 in these cell lines was observed relative to the lead compound, which lacked the appended heterocycle.
