Abstract
Sphingolipids constitute a broad class of compounds with many biological functions. The sphingolipid metabolites ceramide and sphingosine are potent apoptosis inducers and produce cell cycle arrest, whereas sphingosine-1-phosphate promotes cellular growth and differentiation. Herein, the effects of sphingolipids and their analogs on diverse signaling pathways implicated in the apoptotic process are highlighted. The relatively simple chemical structure of these compounds has led to several strategies for their total synthesis. Those methods have contributed to the development and biological study of several analogs that present diverse degree of modification from the original structure. This article catalogues many of the recently developed synthetic analogs that act on diverse aspects of sphingolipid metabolism. A description of known enzyme inhibitors of the sphigolipids pathway is also given. Finally, diverse new sphingolipid-like antitumor agents isolated from marine sources are presented. This contribution opens the way for future development of new sphingolipid analogs that might be useful in cancer chemotherapy.
Keywords: Sphingolipid analogs, sphingosine, ceramide, apoptosis, signal transduction, anticancer drugs, structure-activity relationships, drug design
Current Medicinal Chemistry
Title: Sphingolipids in Anticancer Therapy
Volume: 13 Issue: 7
Author(s): Jose M. Padron
Affiliation:
Keywords: Sphingolipid analogs, sphingosine, ceramide, apoptosis, signal transduction, anticancer drugs, structure-activity relationships, drug design
Abstract: Sphingolipids constitute a broad class of compounds with many biological functions. The sphingolipid metabolites ceramide and sphingosine are potent apoptosis inducers and produce cell cycle arrest, whereas sphingosine-1-phosphate promotes cellular growth and differentiation. Herein, the effects of sphingolipids and their analogs on diverse signaling pathways implicated in the apoptotic process are highlighted. The relatively simple chemical structure of these compounds has led to several strategies for their total synthesis. Those methods have contributed to the development and biological study of several analogs that present diverse degree of modification from the original structure. This article catalogues many of the recently developed synthetic analogs that act on diverse aspects of sphingolipid metabolism. A description of known enzyme inhibitors of the sphigolipids pathway is also given. Finally, diverse new sphingolipid-like antitumor agents isolated from marine sources are presented. This contribution opens the way for future development of new sphingolipid analogs that might be useful in cancer chemotherapy.
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Cite this article as:
Padron M. Jose, Sphingolipids in Anticancer Therapy, Current Medicinal Chemistry 2006; 13 (7) . https://dx.doi.org/10.2174/092986706776055553
DOI https://dx.doi.org/10.2174/092986706776055553 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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