Abstract

The ceramide and sphingoid base backbones of sphingolipids are highly bioactive compounds that offer promise as chemopreventive and chemotherapeutic agents against cancer. The primary goal of this section of our NCDDG proposal is the creation of functional libraries of both naturally-occurring sphingolipids and sphingolipid analogs that can be used in a variety of high throughput screens, as well as in focused structure-function studies for lead optimization. In order to accomplish this, we utilize both solution-phase and solid phase synthesis techniques, many of which have been developed here at Emory over the past decade. As leads are identified, we will also initiate process research studies, the goal of which will be to develop synthetic protocols capable producing the larger quantities of materials required for in vivo evaluation of drug candidates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA087525-02
Application #
6453629
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2001-06-01
Project End
2001-08-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Acker, Timothy M; Khatri, Alpa; Vance, Katie M et al. (2013) Structure-activity relationships and pharmacophore model of a noncompetitive pyrazoline containing class of GluN2C/GluN2D selective antagonists. J Med Chem 56:6434-56
Symolon, Holly; Bushnev, Anatoliy; Peng, Qiong et al. (2011) Enigmol: a novel sphingolipid analogue with anticancer activity against cancer cell lines and in vivo models for intestinal and prostate cancer. Mol Cancer Ther 10:648-57
Pruett, Sarah T; Bushnev, Anatoliy; Hagedorn, Kerri et al. (2008) Biodiversity of sphingoid bases (""sphingosines"") and related amino alcohols. J Lipid Res 49:1621-39
Wang, Hongtao; Maurer, Barry J; Liu, Yong-Yu et al. (2008) N-(4-Hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphingosine to enhance cancer cell killing. Mol Cancer Ther 7:2967-76
Morales, Pablo R; Dillehay, Dirck L; Moody, Steven J et al. (2007) Safingol toxicology after oral administration to TRAMP mice: demonstration of safingol uptake and metabolism by N-acylation and N-methylation. Drug Chem Toxicol 30:197-216
Dougherty, Ann M; McDonald, Frank E; Liotta, Dennis C et al. (2006) Synthesis of 1-deoxysphingosine derivatives with conformationally restricted pyrrolidinediol head groups. Org Lett 8:649-52
Zheng, Wenjing; Kollmeyer, Jessica; Symolon, Holly et al. (2006) Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy. Biochim Biophys Acta 1758:1864-84
Wiseman, John M; McDonald, Frank E; Liotta, Dennis C (2005) 1-Deoxy-5-hydroxysphingolipids as new anticancer principles: an efficient procedure for stereoselective syntheses of 2-amino-3,5-diols. Org Lett 7:3155-7
Symolon, Holly; Schmelz, Eva M; Dillehay, Dirck L et al. (2004) Dietary soy sphingolipids suppress tumorigenesis and gene expression in 1,2-dimethylhydrazine-treated CF1 mice and ApcMin/+ mice. J Nutr 134:1157-61
Sullards, M C; Wang, E; Peng, Q et al. (2003) Metabolomic profiling of sphingolipids in human glioma cell lines by liquid chromatography tandem mass spectrometry. Cell Mol Biol (Noisy-le-grand) 49:789-97

Showing the most recent 10 out of 11 publications