SPHINGOSINE- AND CERAMIDE-ANALOG TOXINS—AN UPDATE

Abstract

The first sphingosine-analog toxin was isolated in 1978 by Carter and Rinehart, who recognized both the analogy to sphingosine and its potential as a mechanism of action. However, interest in the field has expanded greatly since the recognition by Riley and associates that fumonisins, putative environmental tumor promoters that contaminate the food supply of hundreds of millions of people worldwide, are also sphingosine analogs. Sphingosine is a component of sphingolipids, some of which play structural roles (e.g., sphingomyelin), while others (sphingosine, ceramide and glycosphingolipids) appear to play important roles in cellular regulation. Sphingolipid analogs may act by altering normal sphingolipid metabolism, or by interacting as agonists or antagonists with sphingolipid-binding sites in regulatory processes. In the discussion that follows sphingosine analogs are classified as (i) simple sphingosine analogs isolated primarily from marine lower animals and characterized by either primary amines on linear chains or heterocyclic rings; (ii) myriocin-type analogs characterized by a 1-carboxylic acid moiety, which are antifungal agents produced by other fungi; (iii) fumonisins and AAL-toxins, a large but narrowly-defined structural class produced by phytopathogenic fungi; and (iv) vis-1-deoxysphingosines, which a tail-to-tail dimers obtained from marine lower animals. Ceramide analogs are classified as either simple ceramides or glycosphingolipids. These sphingosine and ceramide analogs exhibit a wide range of biological activities.